What's up everyone? It's your girl Kinsey here from Leighton Sports Cards and I'm ripping 2022 tops chrome formula one racing eight box break Number two random teams again. Here's the look at the random results again You can always find these at leightonsportscards.com under the results tab link is also in chat for you Good luck. Here we go. If one has been hot tonight. What's up Ramirez? Bucklist to be one of the one of the commercials. That's awesome What's up Wolf? It's been going good. It's been going good. I'm missing some big hits man. Here we go. Let's see 720 McLaren refractor Charles Leclerc refractor we got purple chicken flag Sebastian Vettel 24 of 199 Aston Martin Got way rave Lewis Hamilton. There you go Mercedes again. The way raves are the light box exclusives So we're looking for here. So a few spots left in number four. That's gonna be the last F1 of the night Alpine refractor Then eight box half case break random teams 99 99 a spot if you're looking for Personals tonight award winners for Red Bull refractor Forest is currently live over on drip. Be sure to check him out No personals on the main channel tonight just over there with him for staff and on the purple 58 of 399 And you can download the drip app or go to the drip shop dot live and then our username there is Layton sports. We've got purple and gold Vettel speed demons Vettel We're looking personals all night there get a new platform that we're testing out here. We got total wolf on the way rave Sam did the inaugural stream last night raconan refractor Did did well. He said so they had a lot of fun over there So definitely be sure to pop in say hi You know if you have any questions about that Druga bitch future stars refractor and Red Bull refractor. We also have Layton gaming over there with Caleb He had a stream going to last night Ricardo on the way rave ripping the new Pokemon the Zenith It's a really cool set. I Don't do much Pokemon, but might need to buy me a box of that looks sweet Signs we've got gold Esteban Ocon for Alpine that is seven out of fifty Nice one there Alpin is Philip R. There you go Philip It's just a different platform to me like we stream here on YouTube and twitch It's just another platform to stream reference sports cards TCG's you do personals There's people who do auctions to sell breaks Botas refractor just a different platform doing the same thing You know since it's newer. There's a less wait time to rip a personal Yuki Sonoda on the checkered flag Just different formats to breaks and things like that Lando Norse on the way rave I would definitely recommend checking it out though. Yeah. Yeah, exactly Exactly like that to me Smaller platform for now All right box to Yeah, he's over there ripping personals all night long on drip again. You can download the drip app Or you can go to drip shop dot live And find us on there We've got Liam Lawson future stars refractor McLaren refractor We got a Daniel Ricardo way rave. I think the game's on I want to try and find it Is this a channel it's supposed to be on Is it Gavra stop and refractor Alpine I'll show you Blake's seat here after this break. Yeah, it's a checkered flag max for stopping No Yuki Sonoda way rave. I mean they're up in price this year just because of a bank arrow Like nosebleeds when the Lakers came we're like three hundred dollars.  Wow before he retired That purple red Conan 205 and 399 We've got orange and red Charles LeClaire we're stopping refractor Latifi way rave Kevin Garnett Paul Pierce refractor Verstappen. What teens you play for play for Dennis Hager refractor purple Checkered flag of Alexander Albonne Williams racing Shaquille and no, he played from one of them future stars Iwasa on the way rave. I don't know. I'm stuck. Oh You didn't like Kobe That was obvious wasn't it?  I know I got I usually get a lot of hate for it But each their own everyone has their own opinion But I mean it's it's it's like what I said he respects Kobe's game He just didn't like him as a kid because he would always beat his favorite team. So like Yeah, I understand but yeah, that's that's a different opinion for sure. We've got way rave of Botas refractor Boschian Yeah Yeah LeBron does not Like I was talking about the other night when they were the Lakers and the Grizzlies were like smack-talking He's like, oh, don't talk smack You can't gar me blah blah blah then literally pressed down on the gas went full court blew by everyone and dunked on him Why can't you do that every time, you know a sergeant refractor? I'm sure he could but he doesn't You know like Doesn't play defense. He cries all the time future stars way rave JQ's That's why I don't like him. I respect his game though. He's one of the best play he is the best player of this generation, but way rave of Steiner for Haas George Russell. I also don't think Kevin Durant gets the Respects that he deserves We got Yuki a nice one there you are sorry Joe Guanyu on the rookie refractor Alpha Romeo A little bit more than LeBron, but not full force, you know 248 of 399 Armory Hordeel He's not afraid to speak his mind though, that's what's different about KD He will straight up tell you to your face, you know Refractor Horner, we've got Greenway rave Sergio Perez 16 of 99 That's what I'm saying. So like if you put LeBron back to play with Dennis Rodman or you know Michael Jordan he wouldn't last 10 seconds Yuki refractory got orange wave Daniel Ricardo for McLaren That's a beautiful color match with the car. That's sick four out of 25 McLaren is Daniel L. Very nice Just on a burger account we'll bag that one We've got rookie refractor Joe Guanyu. Yeah, I did too I played in college like I understand it, but That's funny nice rookie checker flag Joe Guanyu man pulling all the Joe's here I Played out in Nebraska. We got gold and purple Pierre ghastly speed demons Lecler No, just a smaller college out in Nebraska about 45 minutes from there award winners way rave of Mercedes Packbox three I'm Candice Parker Red Bull Refractor. I watched her at Tennessee. I'm a big bulls fan. I was born in Nashville But yeah, I think bulls fan. I love I love Candice Parker.  I like her. I watched her at Oregon I'm excited to see where she lands. I think free agencies started what today or pretty soon for WNBA I know she had meetings with the Liberty self her and I an SQ play on the same team together Boy, that would be crazy. Lewis Hamilton way rave Mercedes Yeah, that was you know, she was amazing coach for a staff and refractor I See his face I have an autograph No for our factor. Yeah, I see his face. Oh my gosh, what's his name? Gino Gino Alpha Tari, we've got purple checker flag of Botos. That's a 189 of 199 I've got an autograph of 8 by 10 of him I have a one of my favorite pieces in my collection. We've got orange in red Lewis Hamilton There you go. It's speed demons Alonzo is assigned 8 by 10 Pat summit Schumacher on the way rave I've got a to Rossi 8 by 10 to signed photo max for staff in I pulled an auto for out of a revolution yesterday And then my amore to like for an $80 box, I need to buy one of those Piazzery refractor purple Sebastian Vettel 189 of 399 Yeah No Lance stroll refractor. We've got George Russell way rave Sick got way rave Lewis Hamilton. I believe they're there used to be a WMV team in Orlando I Remember Mercedes refractor Yeah, wolf. Why is that? One of the cards I pulled we've got Marcus Armstrong refractor Haas refractor I did not check her flag JQ's Van Amster for Cardo and green Felipe drug of itch for MP Motorsports 65 of 99 Again, if you want if you want a personal rip tonight, there's none on the main channel Be sure to go check out forest over on drip He is live on the drip app You can download the app and search latent sports or also go to the website drip shop dot live He is live currently Ripping personal Get you the link here There is a link for the drip Got a bunch of different stuff on on the site that you can Purchase for personal and a Norse refractor got checkered flag Sergio Perez. They were a future stars Roy Nassani Albon refractor is there one you don't like Because if they complain then they're seen differently Yeah, pink wave of Seidel from McLaren 14 to 75. What's the girl's name? She made a Statement the other day the girl who plays for LSU Williams racing mix Schumacher on the Many diamond 840 of 299.   I was raising in Baltimore You know, we played outside you used to smack talking, but if I was a boy, you know you You encourage that but then like as a girl it's seen as Like you're not supposed to do things like that purple and green Yuki Sonoda nice one there George Russell refractor She has a point Yuki nice one there on the way rave for Alphatari Very valid points Kevin Magnuson refractor took away the stipulation for winning championship and gave him a base salary of 76 mil Pay me 76 mil to race a car I know it's a lot more than that, but geez that's crazy Good for him McLaren refractor hell of a driver six the rumors true 681 mil for 13 years All right to me we're not gonna deal with ignorant comments like that Thank you to forgot your yeah, we're not gonna deal with in our comments like that Lewis Hamilton refractor He said she should go make a sandwich Green way rave Sebastian Vettel 79 of 99 Aston Martin. Yeah Yeah, I'm toke on though. Thank you toke. We have Pierre ghastly on the way rape Nicholas Latifi Stappin and Perez Future stars of Dennis Hauger refractor Like Lando Norris way rave have I yeah, no I Probably played I did my freshman year at Daytona State Which is a Juco where a lot of you know girls go that ended up going D1 So I probably played against some good D1 players. I just didn't realize it Aston Martin refractor Six here. Yeah, I would say he's a brand ambassador at that point. Well Absolutely Lewis Hamilton speed demons. We've got pink way rave of George Russell 50 of 75 Mercedes heating up here Nice one there Norris and Ricardo Let's see if we can see Blake He's sitting in like one of those seats. He's not court side, but he's I don't have to look at the thing again Latifi on the way rave, I don't think he's behind the bench I think he's on the opposite side should ask him what he's wearing see if we could see him future stars of Cordillo Yeah, I haven't been I haven't been to a game yet this year because we just had Marley, you know purple Yuki Sonoda I'm 75 a 399, but I told row. We definitely got to make a game before the end of the season I love going to magic games Right yeah, that's another thing to you know Every time on Tuesday Sonny refractor alphatari refractor I was hoping to try and win fantasy this year because we got tickets to the game and 500 bucks to the pro shot But I didn't win For here we've got Alexander Albon on the checker flag. Yeah salmon Yeah, they split it because of the whole game that got cancelled Alexander Albon way rave See I was in Sean so like photo wolf ours like Argentinian Like that week it didn't mess up my matchup We've got Vesti refractor and green way rave Louis Hamilton Mercedes on fire 33 of 99 Next week Ricardo way rave. Oh, yeah, yeah by one speed demons look clear Yeah Yeah, I won in one of my leagues Bucks and that game that got cancelled didn't affect either one of us because we didn't have anyone playing and I blew the guy out So it didn't really matter side al refractor cost refractor Yeah, it's a ghastly way rave Botas and Joe All right box seven here There is the link still spots left in number four just two to go again running the same break back next and then one One more after that with spots remaining 99 99 a spot Get you a random f1 team and f2 team and we'll move into baseball Alonzo refractor and purple pier ghastly. That's 157 of 399 That ray rave way rave of Nicholas Latifi Carlos signs God Sebastian Vettel Checker fly Yuki way rave got a gold wave coming up here Gold wave of Sebastian Vettel and Lance stroll nice one there for Aston Martin on the constructors correlation 34 of 50 nice gold insert there Get everyone be sure to check out Boris on drip. He's ripping personals all night long No personals here on the main channel tonight just over there future stars of Bulu Basi Again, you can download the drip app or also go to drip shop dot live and search Leighton sports We've got mini diamond of Daru Vala Don't believe he's got a cue right now at all and if he does it's very very short So if you order something now and get ripped right away Golden purple Lecler Latifi got way rave pier ghastly the fracter of Esteban O'Conn Norris and Ricardo. Oh Jonathan Isaac's back. I already went to the Lakeland team and then he was back and I didn't realize he's playing again already Tonight Botas refractor Card 42 no, not a variation looks like I think I do that every time I see that card Way rave Lando Norris McLaren after Cole. I like Franz Wagner. He's a good player George Russell We've got gold wave Lewis Hamilton Mercedes 13 of 50 grand pre-winner of Saudi Arabia There you go Mercedes killing it here. We'll mag that one future stars refractor of Fiti Pauly and Ferrari Terrence Ross's wife when I had a Amazon wishlist when I was teaching but like half the stuff off that list for my classroom I Got a gold wave here future stars Jahan Daruvala for Prima racing nice gold wave on the F2 racer 19 of 50 Bill banger in this in this box or this case refractor of her Stappin mini diamond Carlos signs for Ferrari Box, let's see one Way rave Lewis Hamilton stroll speed demons Fractor Haas Yeah, a couple Vettel refractor on my first one was in Jacksonville in sixth grade with my dad Then my fiance and I went a couple years ago and they played in Tampa We've got checker flag future starts Fiti Pauly and then I just took my knees to our first game Preseason they played in Jacksonville Way rave Lewis Hamilton and they played in Miami in October, but I was like nine months pregnant at that point I'm back. We're stopping on the green 94 of 99 It's like let me not go and like get all hyped and like go in the labor middle of a Steelers game Hamilton we've got a Marcus Armstrong refractor and Leclerc signs Really wow purple Leclerc on the checker flag 30 of 199 That's crazy his debut and you're not wearing his jersey purple and green shoe mocker speed demon That's funny way rave of a Mari Cordillo Max for Stappin on the refractor card to this is a Um photo variation there you go Red Bull very nice on the first stop in Who's got Red Bull? That is Daniel L. There you go. Very nice. We'll mag this one for you for stopping photo variation Heck yeah, you can't ghastly We've got Lewis Hamilton refractor Off for a male For what Wolf? Last pack here, then we'll do a quick recap way rave Lewis Hamilton. Oh, gotcha. Yeah We've got green way rave Lewis Hamilton Sebastian Vettel drug of itch and Perez Carlos Sainz our pinks we had Seidel and Russell our golds Esteban O'Conn a Vettel and Shrull on the constructors correlation and our Rivala and then our match cards We had the gold way rave of Lewis Hamilton from Mercedes and the orange color match orange wave Daniel Ricardo for McLaren That'll do it for number two. We got number three coming up in a few. Thanks everyone


Welcome back to exotic wine travel. I am your host Matthew Horky. Hi, I'm Shereen Tan Welcome back to the show today We are getting into some Rhone Reds from Santa Barbara County where I'm excited about this episode you He's really excited. I'm excited too Anyways, but before we get started I want to let you guys know that this video has not been paid for it Anyway shape or form, but if you do find value in these videos, we're shooting on Santa Barbara County Check out our guide to the wines of Santa Barbara County called sipping Santa Barbara Recommend a wines and produce. Let's get in this to this today. We are we Corvina I used the Corvina to access all these wines Corvina Model 2 Elite Thank you Corvina for actually a sponsoring unit unit letting us use it on the show and we poured in these beautiful Gabriel Gabriel Gabriel glass gold edition glasses hand blown There will be a discount code for Gabriel Glass Stemware at the end of the video So Grenache, ooh, I love this grip. I think more than you do Grenache, you know, actually famous for Famous for producing being a big component of the great wines of Shetnaf Which you love, which I like very much, but you know for all Santa Barbara County There's a lot of grapes that do well Probably Chardonnay and Pinot Noir are the most famous in the area But Roan grapes, especially soda and Grenache gaining traction, right? Exactly, especially actually the other day we were talking to our Croatian wine writer friend And when we mentioned that we're doing an episode about Santa Barbara or an episode series He said ooh the zero there is great and I was really surprised I mean, I thought I thought he would say Pinot Noir or Chardonnay But it looks like Sarah and also Grenache heard about it quite a couple of times from other people as well It looks like both grids are gaining traction. What if Miles would have been crazy and sideways about Sarah Grenache? Let's get into the some of the wines today the first one I am very excited about this is the Lumen Grenache 2015 Santa Barbara County This only 600 cases are produced aged in neutral oak But made just in the style of Pinot Noir the winemaker Lane Tonner is one of the first independent female winemakers Here in Santa Barbara, right? Yeah, she just started working with this label. This label is fairly new Crafting some nice wines at low prices. I'm excited to taste this vintage. We have not had this vintage, right? 30 US dollars Let's give this First of all the first thing that I know this is is very Pinot in color. It's very very light I don't know if you can see. Do you know if this is whole class? Yeah, you can see this I don't know if this is whole cluster fermentation I would guess this is whole class. We'll have to get back to that. I don't know Let's give this let's let's uh, let's give this a go first the first Grenache In Santa Barbara County to me depending on where it's going. Whoa Looked out at the look of happy fun. Y'all This is very Grenache very strawberry candy cherry Cinnamon white pepper I get the cinnamon What cinnamon more than the white pepper not earthy like old-world Grenache more bright fruit, but very delicious So like what do you say? But you want to give it what do you think what you're picking up? I'm getting a little bit of a green note to it that I'm still trying to figure out what it is Well, let's give this a little bit ago Nice move in the mouth with good grip and partners This is a wine that's gonna appeal to a lot of people right? It's gonna be a crowd-pleasing wine Lot of juicy red fruit Tannins are easy tans are easy going I get a little bit of a white pepper go for people there's there are complexities here for some people that want them Yeah, but what else do you think the finishes has a little bit of rose note to it as well What are you are you okay on this wine you really enjoy and it's well made wine but for your palette profile you liking it a lot or Happy with it. Okay. Yeah, but I still think that can be great. Yeah, I still think this is very good from Lane Good job. She's got crazy colorful hair for me. I'm 4.0 on this wine. I think it's very good I think for me, it's more of a crowd-pleaser. I think that everybody's kind of gonna kind of like this one I Don't think so Let's move on famous producer Very famous new vintage. This is the Beckman vineyards Grenache from Santa Ines Valley 2016 I 900 cases produced Two different clones. I know this was I know this was aged in neutral oak So let's give this a go. He is Beckman is more famous for his surah. I'm excited I have not had the 2016 Beckman wines are big fruity and bold. I'm excited because I heard 2016 and Santa Barbara was a was a Year where there's a little bit more acidity in the wines. So let's give this a go I believe that in this vintage most of the fruit from this came from his Parisma mountain vineyards, which are Biodynamic, let's give this just exactly the back mended. I remember Yeah, it's like this is right right right through the intensity really hits you in the face You can I can almost taste or smell the food flavor and it travels up by Like to my forehead or something along that line for me This is like extremely ripe strawberry cherry when you say a ton of cherry cranberry Hmm Brown oak smell to it, too This is quite complex is 32 US dollars. This is kind of an entry-level offering Maybe brown sugar Let's give this let's give this a little bit ago. It's very good. I underestimate I have to say Some of Beckman's entry-level wines. I would Beckman vineyards. I was not fans of in the past Like this I got a lot of licorice and white pepper on this this has more tannic grip than the lumen This is good stuff It's to me. This is this is the kind of wine. It's easily gonna get 90-something points I think this is for me 4.2 already and Vivino A little bit more burly I would have to say nice stuff really good stuff You ready to move on? Yeah, let's move on So we have a wine that shireen a winery that shireen is crazy about We have a samsara. This is the Grenache from the larner vineyard 2013 I've loved every single wine by samsara samsara. So basically yeah, you love you love these wine Samsara started by Chad Melville who has moved back on to his family vineyards Melville It's now owned by Joan and Dave Sukutak If I can get that right and they brought on they brought on Matt Brady Who was the former winemaker at Jaffers and they were a long time mailing with subscribers and they plan to keep the same style For samsara wine. So let's give this a go. Shall we? Shireen is a big fan of the samsara single vineyard Pinot Noir, especially the Cargassaki vineyard, right? Let's give this a little bit of a smell here It's so interesting. These three wines are really different These are all totally different. This is This is love. This is Santa Maria though. This is from Santa Maria Valley. For me Santa Maria wines are leaner Lamorra city This is like Australian fans will like it, but it has it's it's not a simple one has complexity This is a more old-worldy. When you say In terms of body the mouth you I haven't tasted it, right? But I would guess this is something in between the two for me. I get a lot of pepper and cool It's all it's almost like if I had strawberries with cool whip And I put white pepper over the top of it with a little bit of earth And this really has the salinity that I get from Santa Barbara County, right? I get mint as well. Yeah. Oh, I Am very excited today. So let's give this a go. Oh, it's peppery What do you think of that one? Oh, this is spicy. Yeah This is so for fans of European European wines little leaner wines I would like about Santa Barbara's the wines are not too big and fruity and over the top, but Man, I don't like I like this wine a lot. You thought for my palette. This is more my style as well There's a little bit of blue food notes to it, too They even took a little bit of a while. I think I'm I'm 4.3 on this wine. I think I think this is really darn good I mean if anyone who doesn't like good, I should totally taste this wine and be your sense. Green Ash Not cheaper at all. This is 40 us dollars with 30 32 40. We had different experiences I don't think with any of these wines are going to be disappointed all good wines, but Wow, anything that you want to add on granache good showing my granache Anything you want to add? Well, we're going to flash the discount code for gabrio glasses on the screen right there There for their their standard art their machine blown glasses And for some of their decanters and I will put the link in the description box Guys, uh, check out our guide to the wines of Santa of Santa Barbara County. Thanks for watching And if you like this episode, please subscribe to our youtube channel exotic wine travel. I will see you at the next episode


This is stock number 9J175, we are here at Summit Automotive in Fond du Lac, Wisconsin, you're new and used Jeep Wrangler headquarters. Today we are checking out this brand new 2019, yes this is a 2019 Jeep Wrangler Unlimited Rubicon. This vehicle has a 2 liter turbocharged 4 cylinder motor, a 270 horsepower. And from this HD video you'll be able to check out the looks of the vehicle, all the options of the vehicle, and hopefully get a really good idea of everything that's associated with this particular Jeep. As you can see it is green, it is the mojito color which they debuted in late 2018. There was some talk that they weren't going to do green for 2019, but this is definitely a 2019 and it is definitely mojito green. This vehicle comes with the BF Goodrich All Terrain LT285 70R17 tires, comes with the 17 inch painted and polished aluminum rims. Has the sport hood, these are the normal bumpers that come with it. Has factory fog lights, the lights in the fenders, and of course the 7 slotted grille. Has the red Rubicon outlined graphics on the side, those are just stickers if you didn't like them you can always take them off. Get the granite crystal Jeep lettering with the red outlines there.  Has the rock rails which are standard on the Rubicon package. You get the red shocks there, the off road shocks. This one does have the tow group so you get the 4 pin, 7 pin wiring, and the receiver hitch, red tow hook on the back. You get a full size spare tire and a backup camera, HD backup camera. Really see, get a good look at that tread there. Back storage area, pretty nice size, and you also have storage underneath here which they brought back. You can put your bolts in there for your roof and your hard top. Also has a spot for your electrical and your windshield washer fluid so that they're not all flopping around. Got, still have 3 bolts on the sides, they made the tailgates lighter, also have your badge on the back of here. And as you go down this side you'll notice you get the trail rated badge, only on the driver's side. Heated mirrors, inside this Rubicon package has the black cloth interior, it has a manual height adjust, got the honeycomb design, red Rubicon lettering and stitching, factory floor mats throughout. This one has auto headlamps. It does have a tilt and telescopic steering wheel. So they started that last year with the JL. And as we hop inside you can see that it has the 7 inch TFT display. Has your digital speedometer, compass, outside temperature display. You get a leather wrapped steering wheel, cruise controls on the right, Bluetooth and audio control or information center controls on the left. Then on the back of the steering wheel there are audio controls. This one has the 7 inch Uconnect radio, AM, FMN, Sirius XM radio capabilities. Also has Android Auto and Apple CarPlay capabilities as well so you can hook up your phone and display your Waze app or Google Maps or whatever you may use. Has your dual climate control, start stop feature, stability control, downhill assist control. You get your power windows down here. You also have your mid-day center for your AUGS USB or USB-C.  Your four upfitter switches, part of the tow group, the eight speed automatic transmission and the four by four shifter on the floor. The design on the seats, they're very comfortable. And the headliner or the hard top piece as I should say, nice eggshell finish. And on the JL they added home link so you can connect it to your security systems, lighting or garage door. And we'll take a quick look at the back seats. My favorite part about the new Wranglers is the back seats and all the room that you do get. You also have latch child safety systems back here. Has a 115 volt, 150 watt plug-in USB and USB-C's back here. These seats do fold down, forex or storage. And that's about all we got on the 2019 Jeep Wrangler Unlimited. Thanks for checking out the video. If you want to make this one yours, give us a call right now,<PHONE_NUMBER>. Thanks for one of our sales associates to make this Jeep Wrangler Unlimited yours today. Once again that number is<PHONE_NUMBER>. Thanks for checking out the video. If you want to check out more, you can go to youtube.com slash summit auto. Remember to like, subscribe and share on this video and all the videos that you see there. In fact, in a second you'll see a link to subscribe to our YouTube channel on your left. A link to more new car videos like this one on your right and if you haven't been to our website on the bottom, a link to this vehicle on our website, click those check us out and we really look forward to helping you with this super clean 2019 Jeep Wrangler Unlimited. Thanks again.


What is going on guys welcome back to the channel and I appreciate you being here. Today I bring you another Destiny 2 Forsaken News leak video. Warning guys, spray us ahead and if you want to go into the DLC super clean then leave now. Ok so today we have news under Blind Wild, the Dreaming City's EP activity, the Prison of Elders Armour set and where it's obtained, details under where the Dreaming City changes, the Taken Sparrow and the quest behind it, new exotics as well as new exotic catalysts and much much more people. But hey guys if you would like to support me in the channel hitting that like button truly helps me out and I do appreciate that support and if you are new around here be sure to subscribe for the latest D2 videos, Forsaken's are around the corner guys and I'm going to be on it like a car bunny. Also stay tuned until the end people to find out about my monthly controller giveaway. So let's get into the video. Ok so let's start with the Prison of Elders Armour set. Now we have seen this from plenty of trailers on this DLC, the Prison of Elders Armour will return or Armour that looks exactly like it. This has led many to believe that the actual Prison of Elders activity will be returning also but this is not the case. According to a new recent data mine, the Prison of Elders gear will be a strike exclusive gear set, here is a good part. We do indeed return to the Prison of Elders within this strike, the strike is called the Hollowed Lair. The strike seems to have, according to these data mines, this Prison of Elders gear attached to this strike as specific loot. Now that is what we are talking about people, if this is true this is something we have wanted strikes to be since day one, day one. Strike exclusive gear, I mean yeah for sure the gear is odd from my previous title but it's a start for multiple reasons, I'm grinding the same strike rather than just for one single item. This I like and hopefully Bungie incorporate more of the same into other and future strikes. More reasons to farm that same strike. So yes guys the Prison of Elders gear will return but it's obtained from the Hollowed Lair strike as exclusive strike gear. Now one big question of, while the Queen Worker's Bolt has also been data mined, it will return my fellow sexy bastards but where will this exhaust be tied to? I was thinking maybe this strike but I think that would probably be a little too much, maybe one of the other two strikes and that including the PS exclusive maybe? We will see people. Okay so we are going to move on and on to the Blind Well. The Blind Well we have seen minute for each other within the Forsaken Trailers, what we saw didn't look cool but even on this it's a little scarce. Today I have you guys covered. The Blind Well is considered their escalation protocol of the Dreaming City, it's this kind of activity. Within this activity you are tasked to clear 10 waves of enemies. Now is it clear if the waves are like the EPs just yet? We will be fighting off enemies and buses in random sequences, much like the EP though. From waves 6 to 9 we will be defending a statue which I believe we've seen within the trailer. Wave 10 will be a bus fight which will be a different bus each week. Upon defeating this bus there will be a chance of exclusive armor to drop and three new Exotic Catalysts. These are Catalysts at the moment we don't know what they are, here's me hoping they ain't the Faction Rally Catalysts but Catalysts from new Exotics. Time will tell people, time will tell. So the Blind Well will indeed be the new EP of the Dreaming City, sounds pretty damn cool to me. I can also confirm people that the Dungeon whatever this place is is not the Blind Well, the other day I posted a massive leak on plenty of new Forsaken things, the Dungeon was mentioned and even I thought then it could indeed be the Blind Well of the Dreaming City but within the date of my files there are separate activities as such. So the Dungeon is not the Blind Well. Okay so let's move on and the Dreaming City itself this place looks not only amazing but it looks full of surprises and hidden things to do and find. Now according to the gaming format a while back the Dreaming City changes each week and according to this leak what they meant is that the taking corruption levels will rise one time per week. There are three levels of taking corruption that affect the whole destination and therefore spawning more taken enemies where they in the first week were not supposed to spawn. In the first week of the launch you should see the Dreaming City without any time affected by this corruption. Sounds super cool, the leak goes on to state once you reach a week three the taking corruption levels will be three and at its highest point. When it reaches this stage you will be able to visit spaces inside the Dreaming City that you previously weren't able to go to. More things to do and find I'm guessing will be unlocked in that third week maybe activities as such you can only do on a third week upon release makes sense timed events lasting a week every third week sounds nice I can't wait people I can't wait. Okay so let's move on. Now the other day we saw a taking sparrow which looked great but to myself and many people it kind of looked like an image from D1 just edited a bit in that photo shop. Well actually it's legit and it's tired to zone. The leak states zone will play a big part in this quest. Yes there's a quest for this specific sparrow from what I can tell the spell has a hidden perk that has not been added to the game yet sounds intriguing people for sure maybe it will be tied to the strike result maybe there's a bigger quest behind this spell which takes us to that strike which is probably the case here. Okay so moving on and the other day I mentioned something of a new gear set called the Reverie Gear. This gear was quite interesting at the time and the lore behind it was fascinating while more details on this gear have been released. Now it isn't exactly said how it's acquired but I do believe it will be the new eververse gear and I believe it's the same for the Titan gear set recently dated mine too called the Scathorn Armor. Now images of these armor pieces can be found linked within the video description if you do want to check them out they are looking great but listen to this there is more to this armor things to do while wearing it take a listen complete the dungeon the shattered throne while wearing a full set of unpurified Reverie Armor this tells me the armor obviously purifies and well maybe levels up become ascendant while wearing a full set of unpurified Reverie Dawn Armor purify all pieces of the Reverie Dawn Armor set very interesting indeed people sounds cool for sure and again what is this dungeon what is this shattered throne I cannot wait to find out. Okay so moving on and the date one also states he has found two new exotics which have not been disclosed to us as of yet meaning we ain't seen them in trailers or so forth and also a new exotic quest coming not being the ace of spades wicked we all love those exotic people we really do moving on people and Toland now Toland for some is a fan fave there is plenty of loans dude you probably know all but here are the basics Toland the shattered was a warlock Sunsinger who studied the darkness and eventually went mad leaving the last city in exile he was an expert on forbidden hive arcany for that reason he was recruited by the praxic warlock Arianna III to be a part of the six guardian fire team who delved into the Hellmouth in search of Crota considering only Ares came back alive he was assumed to be dead though unlike the other members of the fire team his fate was never witnessed by anyone else recently messages purportedly written by Toland have been discovered that indicate he yet survives in the hive ascendant realm he attempts to communicate through the garden by unknown means as he takes a debased joy in speaking again to small human form heads now many think he is dead but in actual fact I don't think he is and although we see Toland speaking in a gaming format on the blind well seen on screen now who to say this isn't another one of those fragments we don't know yet but a dead mind does indeed state that he isn't dead but he doesn't want to spoil the part he plays in the Forsaken DLC so take it with a pinch of salt guys take all this information repeat so to believe what you want but I like the day my info in fact nothing has yet been disproved and to be honest so far only things have been confirmed to be indeed factual and I also believe it to be true and so do many many others but yeah guys a massive new leap video today I hope you enjoyed it if so hit that like button truly helps me out and if you are new around here be sure to subscribe also guys before we go every month I give away a fully customizable controller for either Xbox or PlayStation sent anywhere in the world to be with a chance of winning obviously make sure you're subscribed to the channel drop a like on the video leave a comment down below and follow the Gleam link at the top of the video description it's fast simple and legit guys good luck to everybody who enters on that note guys I am out thanks as always for stopping by I hope you enjoyed the video and hopefully I will see you on that next one


Good morning. Good morning. Well, so I'm just looking at the quizzes, and Johnny and Kim Xerox, the wrong one. So don't worry. We're going to do them at the end. So just, oh, you want it sooner? I can give you the wrong quiz. I've got the wrong one, but it's harder. No. All right. So hang in there till the end. Save your adrenaline. Johnny and Kim are off running as fast as they can, and we'll be back with lots and lots of copies of the newer correct quiz. All right. So what I want to do today is to talk about chapter 28. And chapter 28 is on amino acids, peptides, and proteins. So beautiful chapter, beautiful topic, fantastically important, follows on the heels of carbohydrates, the main classes of biomolecules are sugars, proteins, nucleic acids, and then you throw a few lipids and secondary metabolites like alkaloids and so forth on top of that. And chapter 28 is a wonderful chapter in the sense it tries to cover everything. And the result, of course, is given the limitations of the course.  And so what I've decided to do is really focus on amino acids and particularly peptides from the point of view of synthetic chemistry and not even so much the synthetic chemistry of amino acids. There's some cool chemistry on the Strecker synthesis. There's some interesting stuff in the chapter that overlaps with your biochemistry class on isoelectric points and other aspects of amino acids and peptides. And some of this you'll get in your biochemistry class. But I really wanted to give you my own perspective on this topic. And what I see is really some of the beautiful and profound aspects. So let me start with a simple amino acid structure and then a simple peptide structure. And so maybe for regular amino acids, meaning sort of typical amino acids, maybe the amino acid alanine is sort of the archetype. It's an amino acid and people, because the amino group is at the alpha position, call these alpha amino acids. And as I said, this particular one is called alanine. It's the smallest amino acid with a side chain. Now amino acids of course have amino groups and they have carboxy groups and so they can be connected together end to end. And when you connect them together end to end, you get a peptide, small collections of amino acids containing up to about 40 amino acids end to end are typically referred to as peptides. Larger ones, often in nature, polypeptides have folded structures and are typically referred to as proteins. There's not a hard and fast definition of where the boundary is between peptides and proteins. But usually the emphasis would be on folded structures of biological origins for proteins. So I want to draw out a simple tripeptide and I've just arbitrarily taken three amino acids. The first one is phenylalanine. The second one is isoleucine. And the third amino acid is leucine in this chain. So we call this a tripeptide because it's composed of three amino acids, so peptide or a tripeptide. And the particular name of this tripeptide, if you want to get technical, would be phenylalaninele isoleucine, P-H-E-N-Y-L-A-L-A-N-Y-L isoleucine. All one word, not super important how you name polypeptides. Polypeptides have attracted the attention of chemists for organic chemists for so, so long because these are the molecules of life. And because organic chemistry really is the science of life and its molecules. And some of them are remarkably, remarkably powerful. So for example, the polypeptide oxytocin was first elucidated. The structure was first elucidated and then in a tour de force effort it was synthesized by Vincent de Veniode in 1953. And he immediately, I mean timescale of Nobel Prize has immediately won the Nobel Prize for it by 1955. So it's a NONAPeptide, that means nine amino acids and it contains a disulfide bond. I'll just give you a cartoon of the structure but I want to talk about it. So I'm not going to even draw out all the nine amino acids in it, the N-terminal amino acid, the back end, so this is called the N-terminus is assisting. Sistine is like alanine but with a sulfur instead of a CH3 group and then you run through another four amino acids and then the molecule snakes back on itself. Oops, let me get the structure right here. And again, I'm sort of giving an abbreviated cartoon of the molecule. We have another cysteine, so another CH2S and the sulfurs can link together to give disulfide.  All right, and then we continue through another three amino acids and I'm not going to again draw it. I'll just say three AAs to the C-terminus of the structure and it happens to have an amide group here. And so I'll just write over here C-terminus. So this peptide, in addition to having this fantastic historic importance of being this sort of milestone in synthetic chemistry and a real mark of achievement of what organic chemists can do, also has remarkable biological properties. This peptide is produced by your pituitary gland. It's involved in uterine contractions, in pregnancy and in birth. It's involved in lactation. But incredibly, this is also involved in emotions and pair bonding, in other words love. You know, you say, oh, I'm in love with a person and it's that person and it's you. In the end, it's chemicals in your brain. I mean, this is really scary, you know. It's not you, it's the lack of oxytocin I feel for you. My God, what a deal breaker. There's fascinating literature. I don't want to get started out there. On differences in monogamous behavior among different species of voles, you know, these little creatures that run around on the ground like mice or shrews, and the prairie voles are monogamous. They participate in pair bonding. They hook up for life with a partner and it turns out that ties into oxytocin and a related hormone vasopressin and its receptor levels. So this is incredibly powerful stuff. I'll give you one more example because this is a cool example of the types of things that we can synthesize right now. So the virus HIV, or it's horrible, horrible stuff, the AIDS virus, and one of the enzymes that's essential for its life cycle is called HIV1 protease. And it's a 99 amino acid polypeptide protein. It cuts the other proteins that are needed for the life cycle of the AIDS virus. It's what these powerful drugs against AIDS, the HIV protease inhibitors, work against their molecules that fit into this enzyme and gum it up so it can't cut the proteins that need to. And this protein has been synthesized. It's a dimer, by the way, meaning two halves come together noncovalently, but this protein has been synthesized chemically in the laboratory and what's really cool. Okay, so you'd say, well, great, nature can make this thing too. What's really cool is chemists can make the mirror image of the protein and have used that to discover drugs which is really, really cool where you can go ahead and then use biological techniques to get a peptide that interacts with the mirror image and then you make the mirror image of the peptide that interacts and you've got something that's biologically is functional but doesn't break down. Anyway, incredibly cool stuff. I'm just going to give you a little bit of flavor of things. So there are 20 common naturally occurring amino acids. People often refer to these as 20 natural amino acids. Natural is a little bit of a fake word here because you can find others in nature, but there are 20 that are regularly coded for in the proteins in your body. I'll leave it to your classes in biology to insist that you memorize all of them or memorize the three-letter codes just like what we did with the sugars where I focused on a few sugars. I'd rather you know a few of them. I'll put up more than I think you should know but I want to show you some principles here and show you some of the variations. So a lot of the amino acids have nonpolar side chains. So for example, we already saw alanine with a methyl group and that's kind of the archetype for amino acids is to have a side chain. If you have an alkyl group as the side chain, you describe it as a nonpolar amino acid, right? You've got a greasy side chain. Grease and hydrophobic interactions, the desire to get away from water are a big factor in protein folding. So typically you have more of these hydrophobic amino acids on the inside of proteins. There are all sorts, not all sorts, but quite a number of different alkyl side chains. So for example, alanine is a methyl group, valine is an isopropyl group, phenylalanine is a benzoyl group, leucine is an isobutyl group. I'll just draw out a few of these, leucine. All right, so there are a couple of hydrophobic, a couple of greasy amino acids that are sort of odd balls in structure. Glycine is actually the smallest of amino acids. So glycine is the only one that doesn't have a side chain. So all of the other amino acids have a side chain. They all have the same direction of the side chain. Cysteine, because of the conningold pralogue rules, they're all by the way S stereochemistry. So I'll write S here with one exception. The amino acid cysteine, because of the higher conningold pralogue priority of sulfur ends up being R even though the chain points in the same direction, but that's kind of a technicality. Okay, so this is glycine. So glycine of course is achyro. We don't have a stereogenic center at the alpha position. The other sort of odd ball among the nonpolar amino acids is the amino acid proline. Technically proline gets called an amino acid, but that's not particularly important. What is important is that the amino group in proline is a secondary amine rather than a primary amine. This gives rise to some interesting structural features in proteins. Proline in particular has a tendency to turn back on itself, for example, because you can get cysts and transconformations about the amide group that it forms. All right, so that's kind of a selection of some of the hydrophobic amino acids. I want to show you some of the polar and charged amino acids. So the amino acid cyrene, for example, has a hydroxy group. One of the reasons that we're doing this right now and why you're writing these out is that unless you go ahead and really see things, unless you actually write and think about them, all of this just ends up structures in black and white. So cyrene, if you can't read my writing, S-E-R-I-N-E, is just like alanine, but it has an alcohol group. It has a hydroxy group off of the methyl position. There's threonine as well, which has an extra methyl on there, but I won't write it out for you. So I talked about cross-links from sulfur, and they're one of the important things in protein structure. So the amino acid cysteine is just like cyrene, but it has a thiol group. It has a sulfhydro group. And thiol groups oxidize very well. They oxidize very easily and form disulfide cross-links. And so this ends up, as I mentioned before, with hair and so forth, giving structure to proteins. Not all of the amino acids have side chains that are neutral in water at physiological pH. And again, I will leave it to you and your biochemistry classes to discuss more the charge of amino acids at various conditions. But this amino acid is glutamic acid. You may have heard of it in terms of monosodium glutamate, MSG, and your food in Chinese restaurants. It's the salt of it, gives a meaty flavor to things. And of course, in water, at neutral pH, the carboxyl group, right, carboxylic acids have a pK of 4 or 5. So in water at neutral pH, you're going to have the carboxyl group deprotonated, even if the amino acid is part of a polypeptide, where the amino group and the carboxyl group of what's called the mean chain are part of the polypeptide. The side chain is going to be deprotonated. So glutamic acid is an acidic amino acid. There are basic amino acids. But I want to show you its sister. Its ill-named sister, I might add, another polar amino acid. So we have a primary amide group here. This is called glutamine. Glutamine is just like glutamic acid but with an NH2 group instead of a carboxyl group with an amide group. Now to me, that doesn't make any sense. Glutamine isn't an amine. An amide group isn't an amino group. It's not basic. It doesn't behave like an amino group. But that's its name, and you call it that. There are amino acids with real amine groups here, lysine being one of them, another basic amino acid. And I'll give you one last amino acid. As I said, I'd say this is more than I would expect you to know unless you're a practitioner of the art. But you've seen now examples of all of these functional groups here. And so I think this is a really, really nice introduction to amino acid structure in polypeptide. So lysine, of course, at physiological pH, remember your pKa's, side chain of lysine, it's an amine, pKa's going to be about 10 or 11 so it'll be protonated at physiological pH. Arginine is the last one I'll show you. Also has a basic side chain. It's got a guanidine group. Arginine is even, arginine, arginine, arginine, the side chain's even more basic than an amino group. And so it's going to really be protonated at physiological pH at just about any pH you can imagine. All right, now as I was saying at the beginning what I think is just fantastic is the progress that chemists have made in the chemical synthesis of peptides and proteins. And if you think about it, the way in which one can investigate biological function, for example, the function of oxytocin or the function of vasopressin is to make molecules that have similar structures and say what does this group do? What does the cysteine group do? What happens if we rearrange the structure? And so the chemical synthesis, in addition to being a way of initially proving structure, also ends up being a tremendously powerful exercise in investigating biology. Now the conundrum, if you look, let's take a simple dipeptide. And so if I draw out just a simple dipeptide, I'll say R2 for just a generic side chain and R1 for just a generic side chain. And again, that could be anything. It could be phenylalanine. It could be isoleucine. It could be leucine. So if we look at this basic structure, you say, okay, well it's pretty obvious that the main bond in a polypeptide is an amide bond. You can say, okay, it makes sense if we were to think about how to make this molecule. We'd look at that bond and say we've learned a heck about making amide bonds. We've been talking about carboxylic acid since the beginning of the course in chapter 19 and then some more about it in chapter 22. We'd look and say from a strategic point of view, this is really simple. You'd go and say, all right, we just have to envision making that amide bond. And you know in the abstract in the view at 20,000 feet that we can make an amide bond by the reaction of a carboxylic acid and an amine. And now the problem begins. Well, how do you actually, how do you do this? We've learned lots of chemical reactions. We've learned that under the right conditions, if you go ahead and mix a carboxylic acid and an amine, maybe with a coupling agent, you learned about DCC. For example, you say we've learned ways of making amide bonds. You look at this and you say, yeah, okay, maybe somehow we could envision putting this together. But obviously you've got fantastic problems here. You've got two different carboxo groups, two different amino groups. Even if I threw together one amino acid and the other amino acid with something to make the carboxyl group react with the amino group, you've got a molecule could react with itself. You could get a molecule with two R1s in it or two R2s in it or an R2 at the C terminus and an R1 at the N terminus or the molecule could continue to build a polymer and you get three or four. In other words, you'd get an unholy mess no matter what you do. And we've been talking for the entire class about how organic chemistry is all about control and how organic chemists seek to control how reactions occur and that really boils down to being the essence of the synthesis of peptides and proteins. So imagine for a moment, I'll show you the answer and then we can talk about sort of the whys and so forth. Imagine for a moment we took one of our components and we were to tie up, we were to protect the amino group here. We've already learned about the concept of protecting groups. You've learned for example when you have an alcohol that you don't want to react as an alcohol, you can mask it. You can protect it as a TBDMS ether, a tert-butyl dimethylsilate ether group. And you've learned carboxylic acids don't react like carboxylic acids when they're part of an ester group. So you can envision protecting the carboxyl group as well. And so by being able to selectively protect, to tie up the amino acids, you can achieve this element of control. The groups that are widely used for these types of protection reactions are various esters including benzyl-like esters, benzyl and benzyl-related esters for the carboxyl group. And the T-Boc, tert-butoxy-oxy carbamil and other carbamate groups for the amino group. Let me show you a specific example of just a standard way of putting together a peptide. We'll make valoalanine by this. So imagine for a moment now that we put on valine, your textbook will talk in more detail about how these protecting groups can be introduced. I think in the time we have, I'll simply say it's very easy to take the amino acid valine and react it with a reagent like di-tert-butyl-dicarbonate to go ahead and put on a Boc group on the N-terminus of it. And by various esterification processes, one can go ahead and put on a benzyl ether or a related group to a benzyl ether on the C-terminal group. And I think I said we're going to use valoalanine here. So I will just go ahead and point out that this is, BN is used to abbreviate benzyl group. And we've learned about reagents that can react with a carboxyl group and render it more reactive. So for example, the reagent DCC, I'll show you it in just one second, can go ahead and can activate this carboxyl group and then allow it to react with this amino group. So the overall product of this reaction, and I will now start to use shorthand for these very big molecules, the overall product for this reaction then is the Boc amino valine on the N-terminus, O-benzyl ester on the C-terminus, and I haven't drawn the byproduct of DCC. All right, so just to reduce things, we're going to have to reduce things to a lot of our groups. Let's imagine for a moment that this carboxyl group is the carboxyl group on that carboxylic acid, that Boc valine carboxylic acid. DCC is a diametry agent. We talked about it briefly. Your textbook gives a mechanism for its reaction. It's really not the best way of writing the mechanism, but I think many students would think of the mechanism in the way your textbook writes it. Suffice it to say, cyclo-DCC-dicyclohexyl-carbodi-imid can react with a carboxyl group to give an activated carboxyl group. And the structure that I'm drawing here looks awfully fancy until you think about it. I'll abbreviate those cyclohexyls as CY. This structure looks awfully fancy until you think about it, and then you say, wait a second, for the longest time, he's been saying that a double bond to nitrogen is very similar to a double bond to oxygen. So this structure, this intermediate, this oacylurea intermediate, I'll just abbreviate it as int, is basically like an anhydride. In other words, we have a carbonyl with an electron with drawing group on the oxygen, and so the amine partner, which in this case I will just abbreviate as R prime NH2, now can act that, of course, being the CBC ester of alanine there, or rather the benzyl ester of alanine, alanine-benzyl ester, can react. I won't take us through all of the steps of the mechanism, but suffice to say the first step of the mechanism is the amine, a nucleophile, can attack the carboxyl group of the oacylurea intermediate. Electrons kick up on the oxygen, electrons kick down, they kick out what ultimately is dicyclohexylurea after some proton shuffling, and so the product of this reaction is the amide plus the byproduct dicyclohexylurea. And as I've been emphasizing in this class, organic chemists are very bad about writing byproducts of reaction because they're typically focused on the main product. The byproduct is called DCU dicyclohexylurea. So dicyc, by the way, was the first major coupling reagent that was invented, but it wasn't the last. It's actually terrible stuff to work with. It reacts with the proteins in your body to functionalize them, which sets your immune system on guard against them, which means that after working with it for a while, you'll start to develop terrible, terrible rashes, which is why Johnny and Kim, even though they will synthesize peptides in the laboratory as part of their research on cancer and Alzheimer's disease, never worked with DCC. So here we are at our peptide, and I want to draw out the structure again and talk about what can happen to this because now we have a peptide, we've synthesized a peptide in which our C and N terminus are protected with protecting groups, the benzyl group on the benzyl ester group on the C terminus, the Bok group on the N terminus. The Bok group is labile to acid. That means that a strong acid can take off the Bok protecting group and return to you in a mean, or technically in a mean salt that can be deprotonated. The benzyl group is labile to, among other things, hydrogenalysis. It's also labile to very, very strong acid like hydrogen bromide and anhydrous acetic acid. So if we take our dipeptide and we carry out two deep protection steps on it, a hydrogenal, we'll start with a trifluoroacetic acid deep protection step. This is TFA, I'll write this in parenthesis. Trifluoroacetic acid is a pretty strong acid. It's right on that cusp between weak acid and strong acid, not as strong as HCl, not as strong as sulfuric acid. It's PKA is about 0.23. So it's way, way stronger than a regular carboxylic acid due to the inductive effect of the trifluoro methyl group. And then if we carry out a hydrogenation with palladium on carbon, we can remove both of the protecting groups. And so I'll just remind us, I'll say Bok is able to be removed with strong acid, e.g. for example TFA. And the benzyl group is able to be removed by hydrogenalysis or very strong acid. And as I said, by very strong acid I mean, for example, hydrochloric acid, HCl and dioxane, hydrogen chloride in dioxane or HBr and acetic acid. All right, so the overall result of this is that we have now removed both of the protecting groups to give us just the free peptide like so, in other words, we have hidden one carboxyl group, hidden one amino group, brought together the other carboxyl group and the other amino group and coupled them together. Now I'm lying to you just a hair about this because I haven't used a base. Technically, we'll still be the TFA salt. I'll say it's still the TFA salt at this point. But honestly, if you wanted the free base you could just go ahead and add a base anyway. So technically still the TFA salt. All right, I want to show one thing. We're kind of taking a traipse through mechanism here but sort of mechanism light and getting kind of a summary of how things work. We've taken certain mechanisms in the course and worked them over in gruesome detail like acetyl formation and acetyl hydrolysis which came back to us in sugars. We're getting others where we're getting the general gist of it. Let's talk about the Bokk deprotection mechanism. So okay, so here you have your Bokk group like so. Now in a in strong acid like TFA you can protonate all the different positions in the Bokk group. And the easiest way to think about taking off the Bokk group is if we protonate on this nitrogen here. So I'll write this sort of as a transient intermediate. If we protonate on this nitrogen here now we're all set up to lose a tert-butyl carbocation. And so if we just go ahead and kick out electrons we're going to fragment this molecule into carbon dioxide. Carbon dioxide is very stable and tert-butyl carbocation and an amine like so. And then of course as I was hinting at over here your amine, I'll just draw this down here with more TFA we'll go to RN8, we'll protonate to give the ammonium salt like so. So I want to point out a couple of amino acids that are special. We've already seen them. So we saw for example with lysine you have an extra amino group and we saw with glutamic acid that you have an extra carboxyl group. And so in these amino acids and in several of the other functionalized amino acids, amino acids with acidic and basic and polar side chains, additional protecting groups are needed. And suffice it to say there's chemistry to put on these protecting groups. And I want to stop at this point talking about the details of protecting groups and come on a little bit more to the theory of what we do. So okay, so the general gist of things is we're going to build our peptide amino acid by amino acid starting at the C-terminus and working to the N-terminus. In other words, you could imagine with the valolalanine that we made if we had for example only taken off the buck protecting group off of the amino terminus, we could then go ahead and couple in another amino acid, say phenylalanine, another amino acid say phenylalanine to make a tripeptide. We would introduce that phenylalanine by having a buck group on the amino terminus, on the amino group and a free carboxyl group and again carrying out a DCC coupling reaction. And so this is the type of technology that allowed Vincent de Veniode to build up to synthesize the Nonapeptide oxytocin back in the 1950s and ultimately really create the beginning of a revolution. Now another huge advance came along with an idea that Bruce Merrifield introduced in the 1960s and his colleagues thought he was crazy for this but he won the Nobel Prize in 1984 for what he did. And his idea was to go ahead and connect the polypeptide to a solid support, in other words to make the C terminus of the polypeptide instead of just a protecting group, a big plastic bead. And so let me show you the gist of modern solid phase peptide synthesis and then we can run through a few of the details. So imagine for a moment that we have a polymer bead, polymer plastic polystyrene, I'll show you the structure in a moment and it's not exactly what Merrifield initially used but imagine for a moment that the polymer is basically a big benzoyl alcohol and that you have an OH group on there and then in the first step we couple one amino acid, I'll call it sort of in the abstract, we'll just call it R1 for our side chain and we'll say that we have a protecting group on the nitrogen. So this would be like a buck protected amino acid. And so now we have our amino acid with our protecting group, I'm just calling that PG onto the resin and I'll abbreviate the polymer with this big ball here. All right, now imagine for a moment that we deprotect, in other words we carry out a reaction like the TFA reaction to remove that protecting group for example to remove the buck group that was introduced. At this point you're going to get a, you're going to have the amino group here, the free amino group connected to the first amino acid, connected to the resin which I'm abbreviating as a circle. Now imagine for a moment that I couple in the next amino acid and so I'll say I'll couple and we'll call this R2 on an amino acid again with a protecting group which I will call PG and I think I'll move down to the blackboard here to show you what we've now got. So now we have R2 connected and now we have our protecting group. And imagine for a moment that we again deprotect and now I'm going to shorten things and write deprotect this step one in couple and I'll show you our third amino acid. You notice that we're starting at the C terminus and we're building up toward the N terminus so I'll call this R3 and our structure is getting so big that I now have to go to the other blackboard and at this point we're at a tripeptide now attached and I've gone from the N terminus to the C terminus here with our third residue, our second residue and our first residue. And finally imagine if in the abstract we cleave from the resin and we deprotect, I'll say cleave and deprotect because they're sometimes done at the same time and the result of all of that now is that we have synthesized a tripeptide and the operation is so simple once you work out the chemistry that it can be done on a machine repeating these operations one after another after another to build up polypeptides and even very small proteins purely through chemical synthesis. And this was what got Merrifield the Nobel Prize. It was this recognition that you could do this and the achievement of doing it and so while the work of synthesizing an oxytocin, anonopeptide was a fantastic tour to force, this opened the job to make things trivial to make molecules of that size and one of the beauties of this is you really need your chemistry to work cleanly and so you can use a huge excess of reagents for equivalents of each amino acid to drive the chemistry. Great question. Great question. Why are we going from C to N? And that question is particularly profound when it is counterintuitive when on the ribosome you synthesize it or the ribosome synthesizes the protein from N to C. It turns out that there are reactions that occur. If I try to activate, let's even assume I had this protecting group and I tried to activate this carboxyl group with DCC, there are reactions that occur that will epimerize this stereocenter in chemical environments with vigorous activating agents like DCC so you will get a mixture of diastereomers. So in general, like all the time with certain very special exceptions including something called native chemical ligation that may give rise to the next Nobel Prize in this area. With certain exceptions, with virtually no exceptions I should say, we always go from C to N. The opposite of the way of the ribosome. All right, I want to show you a couple of last bits of the genius that was involved in all of this chemistry. So one of the pieces of genius is really very simple. It's the polystyrene. So polystyrene is a polymer in which you have a zigzag chain of polyethylene with benzene rings attached, like so. You make it by polymerizing the alkene styrene of linking the molecules together one after the next after the next. Now, styrene is styrofoam.  If you do this with a styrofoam cup, then you bring in to lab and you put a little acetone in there, it just melts. It just dissolves technically. So Merrifield's bright idea, one of his bright ideas was to link together two chains with a little bit of divinyl benzene to crosslink the polystyrene into a big network like so so that the chains all link together and the molecule would swell up but it wouldn't dissolve. And then he used the benzene ring and functionalized just a few of the benzene rings on the polystyrene to put on the protected amino acid with the protecting group. So that was one real piece of genius here. And so the chemistry that I've sort of been outlining here really can be thought of as, I'll write this as Bok, let's say for the one that we, or one that we could synthesize, Bok O polystyrene and then we can follow with a series of deprotection and coupling steps where we use TFA, trifluoroacetic acid to deprotect the amino group. And remember I said, well, your amino group technically is still protonated so you can add a base like diisopropyl ethylamine or triethylamine to deprotonate, IPR2NET to deprotonate the amino group that's now liberated and three will couple in the next amino acid. And so I'll say Bok, Phi, Phi is the abbreviation for phenylalanine so I'll say Bok, Phi, OH in DCC. And now we can get Bok, Vail, Bok, Phi, Vail, OPS and we can repeat and repeat and repeat to build up the polypeptide chain, one amino acid after the next, after the next. So I will, I think leave you with, well, let me go ahead and I'll just say repeat and let's say I did this this time with alanine so again it's, we shorthand a lot of stuff here. So let's say I go ahead and do this with, let's say, leucine. So repeat and now we go Bok, Leu, Phi, Vail, OPS and now if you imagine we use a very, very strong acid now we can get a tripeptide and if we had continued on the resin we could have gone up to a tetrapeptide. All right, the final innovation that I want to show you and this is realized, this is standing on the shoulders of giants for many years who made this chemistry possible to a point where it is now routinely possible to make peptides and small proteins. So one of the last innovations was Merrifield's initial chemistry was kind of nasty and by nasty I mean that that last step of deep protecting, of getting rather cleaving from the resin, getting the amino acid off of the resin, getting the polypeptide I should say off of the resin, required super, super strong acid, HBR, hydrogen bromide and acetic acid is one of the reagents used, it's just nasty stuff, anhydrous hydrofluoric acid, anhydrous HF eats through glass, burns through skin, burns to your bone, does horrible, horrible stuff and so the last innovation that I'll introduce was a base labial protecting group, the F-Moc group and the F-Moc group is a big, big, big aromatic unit. It stands for it's in the same family as the Boc group. It's a fluorino methyl, that means CH2, oxy carbonyl and the F-Moc group is cleaved with a base such as papyridine so I'll say a mild amine base and so the F-Moc group if you treat it with papyridine, whoops the base can pull off a proton here, kick out an alkene over here, kick out an oxygen and ultimately kick out carbon dioxide so when this occurs now you end up with the BH plus, the protonated base plus the group that came from the fluorino group which eventually reacts with some more base plus CO2 plus the amine and so putting all of this together I'll just show you an example of a modern solid base peptide synthesis and then we'll wrap things up. So in a modern peptide synthesis what's done is the polystyrene is linked to a much more acid labile linker and this might be a good final exam question to go ahead and explain why this linker here is much more labile to acid and now you have your first amino acid whoops that's a wedge here and so now we go ahead and I'll call this R1 and so we go ahead and we deprotect with papyridine, I'll just abbreviate that as PIP and then we couple and as I said typically nowadays people don't use DCC but I will write DCC so here's our F-mock protected second amino acid R2 and so now you build and build and build and this linker here is called a Wang linker and so I will write O Wang PS and finally after building and building and building you'll cleave with papyridine and so I'll just say repeat, repeat, repeat and then you finally cleave with papyridine, I'll write that as PIP and 2 TFA which cleaves the peptide off the Wang linker to give your peptide. All right well on that note we're going to take a moment to pass around the quizzes so take one minute to finish up writing and then you can put away your notebook.


Live from San Francisco, it's theCUBE, covering DevNet Create 2017, brought to you by Cisco. Hello everyone, welcome back to our live coverage here in San Francisco for Cisco Systems, inaugural DevNet Create event. I'm John Furrier, SiliconANGLE, my co-host, Peter Burris, head of research at wikibon.com. Our next guest is Jose Bergarin, Chief Innovation Officer, all those consulting VIP here at Cisco DevNet Create, welcome to theCUBE. Thank you, thank you. So to tell you a story, you have a really special story of true transformation where DevNet and being a developer in this new world order, has changed things for you. Yeah, actually the people from Cisco call it a racks to riches story. Basically, well I founded my company 10 years ago with my brother and a friend, and business was going good, but we were having some trouble competing with the larger Cisco partners in Costa Rica, so that's why we decided to do something else and software was a way to go. So three years ago I had the opportunity to participate in the first DevNet zone in Cisco Live in San Francisco 2014, and that really was a turning point for my company because we actually shifted our focus to software and software development, and that really pushed us forward and really allowed us to compete with those big partners, but also expand our business to some other parts of Latin America. So now we're doing stuff also in Mexico and doing stuff in Peru, and even thinking about coming to the States and do some software development here. Like taking over the world. So take us through specifically the inflection point. Obviously DevNet, you had an internal compass, you felt it, kind of the tailwind, the marketplace, pretty, pretty, not obvious to everyone, but you guys saw it. What was the moment where you go, wow, we're on to something with this? Yeah, it's probably hard to say because it lasts like different moments. The first one I think it's really Anderson Hurwitz. Andreessen Hurwitz? Yeah, exactly. Adventure Capitalist. Yeah, reading their blog post about software is in the world. So that was a blog post in 2011, I think. But we read about it in maybe 2013, and we started thinking, hey, maybe the way to go is actually to do some software by ourselves and figure out if we can actually improve the Cisco solutions that we're selling right now using software. So we basically used that, and then we came to the San Francisco 2014 DevNet zone and said, hey, now Cisco has a program around this. So maybe, yeah, software is the way to go. Maybe software is the way to actually go ahead and innovate and do some other stuff to better serve our customers. So that's when we actually went back home and doubled down on our strategy and started developing more software and having more conversations with our clients that we were able to solve using Cisco technology and Cisco hardware, but also develop software around it. Why did customers resonate with your story? It was because you had a unique differentiator. What specifically did you do with Cisco that made it such a high impact value proposition? Okay, one of the things that I really like about Cisco is they have a very robust infrastructure, but it's sometimes, or you need special integrations to really solve a business in it for a customer. So a lot of customers that we had really had maybe the hardware or the platform, for example, the Cisco Contact Center, but there's a gap between having the infrastructure and really solving that business need. So when we got there and told them, hey, maybe we can have those skills or we are building those skills in our company to bridge that gap, that really make a difference with our customers. And that's our whole business in the past three or four years has been around that, basically. And so it gave you an opportunity to get into that market. Yeah. And just have good product. Craig, what was the biggest learnings that you've had over that journey? What's the learnings you could share with folks watching? Okay. The first of all, it's a complete shift in your company. I mean, if you've been selling hardware and now developing software, two different worlds complete. I mean, I don't want to say it's easier to sell hardware, but it's maybe more complicated to develop software. It has to be a whole different process because when you're selling hardware, you're basically doing the design and then just like buying this hardware from Cisco and then selling it to your customer. But when you're developing software, you have to have your team ready, develop probably three, four, five months or even six months in advance and then get that solution to the customer. So it takes a while and you have to change all your business. You have to change your practice. It's difficult. I mean, I know that a lot of partners are trying to move in that way and develop more software, but to be honest, it's not that easy. You have to have a lot of commitment from management to actually make it. But I presume you're developing software not just for the hardware in terms of management or something like that. Are you also looking at Webex and Telepresence and the full suite of Cisco products as you start thinking about how you're developing solutions for your customers? Is that kind of the direction you're taking? Obviously, on top of the hardware. Is that kind of the direction you're taking? Yeah, we actually started more around Contact Center and then mainly around collaboration. So Webex, Telepresence, and now even Cisco Spark. And that was our focus for the first maybe three years. And now we're starting to do stuff around networking, like, you know, traditional networking, like router switching, or stuff like APKM, or CMX for the wireless part, or even Maraki gear. So we started in collaboration, but now we're expanding our business to other parts within the Cisco portfolio. And as you think about this message of how the network, which is now becoming programmable, in other words, you can use software to define and reconfigure, rapidly reconfigure the network. Are you also then seeing yourselves working not just with the traditional network people within the companies that you're selling to, but also developers and showing how the network is offering a more superior or extending the quality of the target that they're writing to as they write software? Yeah, yeah, and it's quite interesting. Again, coming from that contact center side, our conversations moved from IT to the supervisors and supervisors in the contact center. And now going to networking, we'll probably have to move the conversation from the operations team now to the development team. So when you start developing software, you actually have to go to the line of business or to teams different from the operational team that you're used to talk to. And I was going to say that's probably one of the reasons why it becomes more complex. That the change management challenges and a partner has to fit into those for installing a new switch or installing a new router is one thing. But the change management practices of going in and evolving the way a contact center operates, and I know Costa Rica is one of the places where at least here in the US, it serves Spanish speaking communities here in the US, that's a pretty significant challenge. There's a lot of change management things that have to happen there. To be dragged into those is not a trivial exercise. But it also points up the need for more intelligent, higher, more easy to manage, more robust types of networking interfaces. Where do you see the network going as a resource for developers to hit? I got to say that it has to become easier to program the network because right now you have a lot of technologies, but they're still not there yet. They're still need a lot of network background to actually use them. And some of them are not very flexible. So those technologies need to evolve for the developers to actually use them. And I see that coming in the next few years and Cisco's made a lot of progress in that. And also what we're seeing is that need to improve the analytics and the information that you can get from the network. And again Cisco, for example, has made a lot of progress in that. More app dynamics. Exactly, exactly. With things like app dynamics or for example APIs like data in motion or the whole computing process that they have. And that needs to improve for the developers to actually start getting more use about it. What's next for you now that you see DevNet create? They're putting their toe in the water or doing a good job here. First inaugural event. Yeah. Does this have legs? Yeah. Yeah, yeah. I mean, I've seen it. I wasn't there in the first DevNet zone in 2014. And I've seen the growth from 2014 to 2015 in San Diego and then Vegas and then Vegas this year. So I've seen that grow in the DevNet zone. I'm completely confidence that the DevNet create is going to get bigger and bigger in the coming years because I've seen how other teams, networking teams, operational teams like people from data center, traditional like compute teams. They're starting to get more interested in software development and events like this. So based on your first signals of the first year at DevNet which you walked in and transformed your business, you feel a similar vibe here. Oh yeah. Yeah, totally. Yeah, completely. You get that vibe of people learning, people starting to say, hey, Cisco's really actually sponsoring this and it's actually putting their money and where the amount is. They're actually investing. And the content's good. I mean, that's to me, the tail is the content. It's called walk in the walk. Yeah, exactly. Man, they're really, really helping the developers and you can see that. Well, let's hope that it translates to the core of Cisco because it's a huge company. I mean, the network engineers in the past, their diversion of developer was using voiceover IP.  Not over, but it's subsumed by cloud, right? I mean, cloud is changing everything. So what are you most excited about right now? As an entrepreneur, recovered, you're back on your way, rags to riches, talking to town. As you look out on the horizon, next, the 20-mile stair, what are you excited about that are enabling you to go out and continue to do what you're doing? What technologies? Yeah, well, probably, I know that some of them it's like buzzwords, like IoT and cloud and machine learning on even blockchain, but actually having those technologies at hand and it's not like you have to choose every one of them, but actually use them, some of them to actually build a better product or better service to your customers. It's something that really excites me. And again, it's something that Cisco's really investing in. So getting the traditional Cisco knowledge, like networking or contact center, and actually improve those technologies with machine learning or some IoT technology, I think that's the way forward. And we're actually doubling down our investment in those technologies. Hosey, thanks so much for coming on theCUBE, sharing your story, really appreciate it. Congratulations. Thank you, thank you so much. And you got to get us down to Costa Rica. Sure, every time. We got to get down there. Heather Palo Alto goes down there, so we might as well, Peter. Seriously, thanks for coming on. Great, great, great to have you. This is theCUBE live coverage in San Francisco for Cisco's inaugural event, DevNet Create Building On, the popular only three-year-old DevNet program. I'm John Furrier with Peter Burris with theCUBE. Stay tuned for more live coverage. Stay with us after this short break. Hi, I'm April Mitchell, and I'm the Senior Director of Strategy and Planning.


Good morning, John. I've been spending a lot of time going through the archives of the Vlogbrothers channels as we're doing our This Day in Vlogbrothers Things. Link in the description to that if you're curious what I'm talking about. But I noticed that the vast majority of Question Tuesday videos, they go to you, John. And while this makes a certain amount of sense, because you make videos on Tuesdays, I think it's a little bit unfair. So today is Question Tuesday on a Friday. I ask people on YouTube and Facebook and Twitter to ask me hard questions. And here's the ones I got. Are you going to answer this question first? Joe, that was pretty easy, actually. What is the new Republican health care plan all about? Well, this is a hard one. Because there isn't a new Republican health care plan. They just want to keep all the good parts of Obamacare but make it cost less by waving their hands around. But if you want to get a little bit less of a partisan hot take on this one, health care triage has an amazing and in-depth video on this. Is flying to space the fastest way for Superman to fly? You know, I don't know too much about the physics of how Superman's supposed to work. So if, like, if air resistance is a really big deal for Superman, then maybe. But my feeling is that air resistance probably shouldn't matter to Superman too much. Just now he's going to get too hot. He seems pretty impervious. So probably know it's going to take longer. Like the further your radius is, the longer your circumference is. That's how circles work. But I am not Superman's keeper. He can do it however he wants to do it. How do you properly pronounce thistle?  I don't know how to pronounce anything. Every time I get a little bit confused, I just open up this app. How'd Jay say? He's just a man who happens to have said like every word. So what, I mean, what do you want Jay to say? Sorry Jay, you're my whole world. Thank you for doing that great work. When people come to VidCon, do they typically rent a car? I don't know if they do but they shouldn't because parking in Los Angeles is terrible and so is driving. Get a cab to your hotel, you can probably walk to the convention center if you need to, you can get an Uber anytime.  Annalise, I'm a huge connoisseur of pears. I love them all. Sometimes I want to get it all over. Sometimes I want that. But if I don't, I get out our nice sharp knife and I just swoop right down and I make a little square of the core and then I'm like nibble on the core.  Get to clean the knife and also maybe your plate that you put them on. But it's such a wonderful ritual way to spend time in the feeling of the knife going just like so through that soft, soft Bartlett. Yeah. I may get too excited about pears. I just realized that for the first time. Would Bernie have one? For this question, let's have a guitar. Well, I don't know when nobody else does it if you think that you're sure then you're wrong. It's too easy to be certain of things that can be proven. So when you feel that way, sing this song. How's Dave? Well, if you're talking about the fish, Dave is less, less good. He could barely hold up his own string, but he's still floating. How many cats is too many cats? Well, according to my cat, two cats would be too many cats, which is terrible for me because my actual answer is like maybe eight. I like cats and pears. Cat by an apple, apple pear. Is the S or the C silent in scent? Oh, that's weird because scent and scent and scent are all words. All right. I looked it up of the online etymology dictionary says that the C and to scent was added in the 17th century because people felt like it. So it's the C. I think that's silent. Can this be the last question? Yes. I have here with me additionally, a bunch of the Prince that Claire Emery made for us to celebrate our 10th year anniversary on YouTube. Hello llama. Yeah. I got Claire to clone me this so that I could show it off. This is the actual wood block that is put into the press and these actually degenerate as they are used.  So when you do wood blocks, it's it's definitely a limited run. I love them. They smell good. I didn't know that they would smell good, but that's the thing. I'm I just wanted to show you me holding them in real life so that you could see the paper and what it looks like and how big they are and stuff. There's a link in the description if you're interested in these. Thanks for all your questions and John. I'll see you on Tuesday.


President Mohammad Buwari has congratulated Governor Billu Matawali of Zamfara on his defection from the People's Democratic Party to the all-progressive Congress. According to the president, the ruling party is becoming more popular because of its impressive record and commitment to good governance. President Buwari's message was delivered by Boss Mustafa, the Secretary to the Government of the Federation, SGF, at the defection in Gousseau on Tuesday. The president urged APC governors and elected lawmakers across the country to continue to work harder to ensure the party maintained its popularity and retained power beyond 2023.


I was so excited to receive a letter by the European Space Agency and the European Commission proposing that Sentinel-6A should be Sentinel-6 Mike Freilich. Having a satellite named after you is pretty remarkable. It's not something we do in Earth science very often. It's not only ESA, it's Europe who wishes to honor Mike Freilich. Mike Freilich has been instrumental in making Sentinel-6 a satellite that measures with very high precision sea level rise. The Sentinel missions are something that Mike was very involved in. It really epitomizes the role that Mike has played over the years as championing partnerships, championing collaborative investigation of the Earth. Names are reserved for the greats. You don't name after a satellite after somebody who just does the job. It's the second mission ever named after a person who's alive. It's a huge honor and I couldn't be more excited. Through this we want to pay tribute to a unique cooperation between the US and Europe and a unique personality, Mike Freilich. Dr. Mike Freilich is a world-renowned ocean scientist who after a successful career in academia came to NASA and for a dozen years let all of Earth science. It has really brought NASA back on the international stage. The partnerships that we forge are beyond a business transaction. They are about friendship and Mike did just that. Working with our international partners, working with our interagency partners. And Mike brought that community together in a way that was really unprecedented. Mike Freilich's legacy is being able to build the coalitions that are necessary for us to get as much understanding of our planet as possible. There is not another person more deserving of this honor than Mike Freilich. You know, when I first found out that Mike had cancer, I got a call from Thomas Erbuchen. So I called up the administrator and told him about it immediately. And he shared with me kind of what was going on and I asked him, I said, we've got to do something quickly. I want him to know that all the work he's done is extremely meaningful. Mike is a leader to all of us and a mentor and a person who has really advanced Earth science for the entire world. What is unique with Mike is his commitment to science and cooperation, but also his resilience and sense of humor. And I believe these are two facets of the same coin. It's unapologetically excellent. I am much better because of what I learned from him and because I had the opportunity to work with him. It's just been very rewarding, not just for me, but for the people in my organization to have had the privilege really of being his colleague in front. He was absolutely committed to dispassionately following the science. He had high standards for himself and everyone around him. Mike had a very big, very full red pen. Everybody was always afraid of that red pen. His pretty intense energy, one of the characteristics was the bouncy knee, which you'd never missed and it was always there and you could kind of gauge the way the medium is going by the pace of the bounce. I have a lot of hilarious emails on my smartphone exchange with Mike, which I keep as a treasure. And thank you, Mike, for being such a wonderful partner, a trusted partner who has built up this relationship over many years without you, Mike, or without Mike Freilich, this would not have happened. It is a no-brainer that we all came together and that they were able to really value out and allow the renaming of Sentinel-6A after Mike. When I got that letter, the first thing I did is, frankly, I called Mike and said, I received this letter. It would be an honor for all of us if we could name that spacecraft after you. Would you accept that? And he said, I'll be selfish, absolutely. I knew in 10th grade that I wanted to be a near-shore oceanographer. What has driven me is understanding how nature works. I got a call from Dr. Jack Kay here at NASA Headquarters asking me whether I might be interested in running the Earth Science Division here at NASA. We made dramatic progress in the last 13 years with our really substantive mission and analysis international collaborations to bring together people who have expertise in many different disciplines to work for long periods of time on problems that none of them individually could solve, but together could. Earth System Science is bigger than any particular agency. It's bigger than any single nation. It's bigger than any single continent. And I surely hope, because humanity requires it, that we make some significant progress in understanding.