Lecture 18. Amino Acids, Peptides, and Proteins.


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Lecture 18. Amino Acids, Peptides, and Proteins.
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Nowick, James
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This is the third quarter course in the organic chemistry series. Topics covered include: Fundamental concepts relating to carbon compounds with emphasis on structural theory and the nature of chemical bonding, stereochemistry, reaction mechanisms, and spectroscopic, physical, and chemical properties of the principal classes of carbon compounds. Index of Topics: 2:49-Amino Acid Structure 5:55-Examples of Polypeptides 12:18-20 Common Amino Acids 17:03-Polar & Charged Amino Acids 22:35-Chemical Synthesis of Peptides and Proteins 27:49-Protecting Groups 31:54-DCC 40:07-Boch Deprotection Mechanism 42:44-Special Amino Acids 43:33-Additional Protecting Groups 46:42-Modern Solid-Phase Peptide Synthesis 54:20-Boch Opolystyrene Example 59:54-Fmoc Group
born and wealth have so so I
just looking at the at the quiz is and Johnny and Kim Xerox the wrong 1 Soward don't worry we're going to do them at the end of the disco hall hall he wanted so I'll find getting the role on wrong Queer as that got the wrong 1 but it's harder I I know you are a sign that the hang in there till the end say saying you're saying your adrenaline Johnny and Kim off of running as fast as they can and will be back with lots and lots of copies of the new where correct itself what I wanted to do what I want to do today is to talk about Chapter 28 in 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 hard sugars proteins nucleic acid and then you throw fuel lipids and secondary metabolites and like alkaloids in and so forth on top of that in Chapter 28 is a wonderful chapter in this sense it tries to cover everything and the result of course is given the limitations of the costs if I don't cut it down we will cover nothing and so what I decided to do is really focused 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 the some chemistry on the Strecker synthesis there's some interesting stuff in the chapter that overlap with your biochemistry class on my soul electric points and other aspects of amino acids in and peptides and some of this still 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 8 simple amino acid structure and then a simple peptide structure in so many maybe for regular amino acids meaning stored in a typical amino acids may the amino acid Alan not alanine is sort of the archetype its amino acid In people because the amino group is that the Alpha position called the EU's Alpha amino acids and as I said this particular 1 is called alanine it's the smallest amino acid with the side chain now amino acids of course have amino groups and they have her boxing groups and so they can be connected together and to end and
when you connect them together and and you get a peptide small collections of amino acids containing
all of up to about 40 amino acids into a new 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 boundaries between peptides and proteins but usually the emphasis would be on folded structures of biological origins for proteins so I want to drive out a simple try peptide that just arbitrarily taken 3 amino acids the first one is phenylalanine the 2nd 1 is ISO Lucena In the 3rd amino acid is Lucine in this change so we call this a try peptide because it's composed of 3 amino acids so kept her eyes were trying peptide in particular name of this tried peptide if you wanna get technical would be fennel Alan Neal ISO Lucine PHE and 1 a L a L a N Y U L I said Lucien all 1 word no but not super
importer's how you name how you name Polly peptides have attracted the attention of for organic
chemist for 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 acts Seto said 1st elucidated the structure was 1st elucidated and then in a tour de force effort it was synthesized by Vincent of in 1953 and he immediately I mean time of Nobel Prizes immediately won the Nobel Prize for it by 19 55 so it's an known peptide that means 9 amino acid and it contains a advice sulfide bond the other stimulant cartoon of obvious structure but I want to talk about it so I'm not going even drawn out all the 9 amino acids in the N-terminal amino acid and not in so this is called the Asian terminus he is assisting in the Sistine is like alanine but with a sulfur instead of a CH 3 groups and then you were under the rule another 4 amino acid and then molecule snakes back on itself With structure right here and again I'm certain giving an abbreviated cartoon of the molecule we have another sustain so another C H 2 S and the sulfurous can link together to give dice sulfide sulfur linkages if your hair gets phrasing for review on curl your hair with a curling iron ore with straightening solution and that it locks back in with curls and it's all linkages in Europe here that actually locked locked in that structure because of course Harris carries protein are right and then we continue through another 3 amino acids and I'm not going again brought all 8 3 days Tennessee terminus of the structure and it happens to have an animated group here in solve this right over here see terminus itself this peptide in addition
to having this fantastic historic importance of being this sort of milestone in synthetic chemistry in a real mark of
achievement of water organic chemists can do also has remarkable biological properties this peptide is produced by Europe pituitary gland it's involved in uterine contractions in in pregnancy and birth it's involved in lactation but incredibly this is also involved in emotions and pair bonding in other words long you know you say Oh I'm in love with a person and it's that person and it's you In the end its chemicals in your brain I mean this is really what this is really scary you know it's not you know it's the lack of oxytocin I feel for you my got what it I wanted deal what a deal-breaker this fascinating literature I don't wanna get started out there on differences in monogamous behavior among different species of bowls you know these old creatures that run around on the ground like Meister shrews and the prairie voles are monogamous state participating pair bonding they popped up for life with a partner and it turns out that ties in Toxey Towson and related hormone vasopressin and its
receptor levels so this is incredibly powerful stuff I give you 1 more example because
this is a cool example of the types of things that we can synthesize right now so the virus HIV neighbors horrible horrible stuff the aids virus and 1 of the enzymes that's essential for its life cycle was called HIV-1 proteges 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 staged aids the HIV produce inhibitors work
against the molecules that fit into this enzyme and dumb it up so we can cut the proteins that need to end this protein has been synthesizes the
diver by the way meaning to have together non-covalent only by this protein has been synthesized chemical in the laboratory what's really cool OK it's a well great nature could make this thing to know what's really call is chemists can make the mirror image of the protein and have used actor discovered drugs which is really really cold where you can go ahead and then used 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 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
29 ,comma naturally occurring amino acids people often refer to these as 20 natural
amino acids Natural's a little bit about of us a fake word here because you can find others in nature
but the 20 that are regularly coded for being the proteins in your body leave that you're classes in biology to insist that you memorize all of them were memorize the three-letter codes just like just like that like we did with the sugars were I focused on a few sugars and brother you know a few of them output of more than I think you should know but I want to show you some some principles here can show you some of the variations so a lot of the amino acid have no polar side chains of for example we already saw Alan the methyl groups and that's kind of kind of the archetype for amino acids is to have a side chain if you have and how side chain described it as a non-call amino acid like you've got a greasy side and hydrophobic interactions with desire to get away water from
water a big factor in protein folding so typically you have more of these hydrophobic amino acids on the
inside of proteins there are also lots not all sorts but quite a number of different alkyl side chains of for example Al-Amin as a methyl group is a probable group phenylalanine is a Denzel group losing is and I of group urges draw out a few of these UCI is the name of the file of the all right so there are a couple of
hydrophobic a couple of greasy amino acids that sort of oddballs and structure glycine is actually the
smallest of amino acids of glycine is the only 1 that doesn't have a side chain so on the other amino acids have a side chain they all have the same direction of the side chain Sistine because of the the con Ingle log rules there all by the way S stereo
chemistries all right last year with 1 exception the amino acid assisting because of the higher conning trialogue priority of sulfur ends up being or even know the chain points in the same direction but that's
kind of a technicality OK so this is glycine scene of course is a prime role we don't have a sterigenics center at the Alpha position the other sort of oddball among men on polar amino acids is the amino acid trolling technically crawling gets called in the answers but that's not a particularly important what is important is that the amino group controlling is a secondary meaning rather than a primary meaning this gives rise to some interesting structural features in
proteins probably in particular has a tendency to turn back on itself for example because you can get system trains confirmations about the intimate group that it forms are so that's kind of a faith selection of some of the hydrophobic amino acids I want to show you some of the other coloring charged amino acids so the amino
acids searing for example has a hydroxy group 1 of the reasons that we're doing this right now and while you're writing these out is that unless you go ahead and really see things
unless you actually write and think about them all at this distance of
structures in black and white so searing if you can't read my writing as and he is just like alanine but it has an alcohol Rupert as a hydroxy group off of the Mathilde position which the as well which has an extra there but I won't write it out for you so I talked about crossed from sulfur in there 1 of these the important things in protein structure so even outlasted Sistine he's just like series entitled has a firewall group has a sulfide
rogue group and file groups oxidize very well they've oxidize
very easily informed crossed lines and so this ends up as I mentioned before with parents so forth giving structure the proteins not old of the amino acid have side chains that are neutral in water at physiological pH and again I will leave it to you in and that 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 soap monosodium glutamate MSG in your food and Chinese restaurants in the salt in it give the meaty flavor to things and of course in water a neutral pH the carboxyl group provide carboxyl Aghazadeh said at the therefore 5 so that water at neutral pH you're going to have the carboxyl group Deep Throat made even if the amino acid is part of a polypeptide where the amino group in the carboxyl group of what's called the main chain are part of the polypeptide side chain is going to be but so glutamic acid
is an acidic amino acid there are basic amino acids but I want to show you it's sister it's
only sister I might add another polar amino acid so we have a primary and group here this is called glutamine glutamine it's just like glutamic acid but with an NIH to group instead of a carboxyl group within and the group now I demand that doesn't make any sense glutamine isn't the enemy and my group isn't at amino group it's not based doesn't behave like an amino group but that's its name and we call it that there are amino acids with real amino groups here lysine being 1 of them another basic amino acid and I'll give you 1 last amino acid as I said I'd say this is more 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 acids structure In polypeptides so lysine of course of physiological opiates remember your PTA His side chain of
lysine its enemy in the case can be about 10 or 11 so we'll be protonated physiological create
Argentina is the last 1 also you also has a basic side chain it's gotten 1 Indian group Argentina's Eva a R G I and II and III Argentina side chains even more basic than amino group and so it's going to really be protonated physiological pH at just about any pH you can imagine are right now as
light I as I was saying at the beginning of what
I think is just fantastic is the the progress that chemists have made in the chemical synthesis of peptides and proteins and if you think about it the way in which 1 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 is this group you what is the Sistine group do what happens if we arrange rearrange the structure and so the chemicals in fish into being a aware of initialy proving structure also ends up being a tremendously powerful Lexus exercise in investigating biology now the conundrum if you look let's take a simple died peptide and just a simple peptide Allstate or 2 the word just a generic side chain and Aura won for just the generic side chain and the again that could be anything it could be phenylalanine it could be I we receive it could be losing something a lot of this basic structure you say How can well it's very obvious that the main bonds in a polypeptide is and hammered bond you can say OK it makes sense if we were to think about how to make this molecule we look at that bond and say we've learned that fact about making bonds we've been talking about carboxyl against said since the beginning of the course in Chapter 19 and then some more about inches to 22 we block and say from a strategic point of view this is really suck balls you go inside are right we just have to envision making that ended bond and you know in the abstract in the you at 20 thousand feet the we can make another bid bonds by the reaction of a carboxyl like acid and enemy now the problem begins well how actually How are you
doing this we will learn lots of chemical reactions with warned that under the right conditions if the
dollar ahead and mix of carboxyl like dancing didn't mean maybe with the couple engaging you learned about the C-17 ha example we've learned wariness of making and Bondsteel look at this and say I'll tell you the somehow we didn't envisioned putting this putting this together but only a slight
obviously you've got fantastic problems here you've got to different carboxyl groups to different amino groups even if I'd
thrown together 1 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 can get a molecule with a two-hour once in for 2 are chosen or art show at the end at the scene terminus in at the end terminus or the molecule could continue to build a polymer you get 3 or 4 in other words you get an unholy 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 chemist seek to control our reactions occurred and that really boils down to being the
essence of the synthesis of peptides and proteins so mentioned for a moment I'll show you the the the answer and then we can talk about sort of the the wise and so forth and mansion for a moment we took 1 of
our components and we were to tie-up we work to protect they amino group here regarding learned about the concept of protecting groups you will learn for example when you have an alcohol that you don't want to react is an alcohol you can mask you can protest protected is a TBD Yemassee Richard metals I'll leave the room when you've learned that carboxyl again acids don't react like carboxyl icon since when they're part of an ester groups you can envision protecting the carboxyl group is well and surrounded by being able to selectively protect the tie up the amino acid you can achieve this element of control groups that are widely used for these types of
protection reactions are various asters including Denzel like asters pencil and bans all related esters for the carboxyl group and the tee box church the taxi oxycodone meal and other car bandmate groups for the amino group let me show you a specific example all just a standard way of putting together a peptide will make available
alanine Biden so I mentioned for a moment now that we put on on the Elaine is a textbook will talk in more detail about how these protecting groups can be reduced I think at that time in the time we
have I'll simply say it's very easy to take the amino acid veiling and reacted with a reagent like Dieter you'll die carbonate to go
ahead and put on a pot group on the and terminus of it and by various US verification process 1 can go ahead and put on a Benthall ether or a related group to avenge the heater on the C-terminal group and I think I said we're going to use available alanine here so I will just go
ahead and point out that this is being here and that is used to abbreviate Denzel
group and we've learned about reagents that can react with the carboxyl group and render it more reactive so for example the reagent DCC also you it just 1 2nd can go ahead and get activate this
carboxyl group and then allow it to react with this amino group so the overall product of this
reaction and I will know start to use shorthand for these very big molecules the overall product for this reaction then it is the box amino daily and on 1 in terminus all Denzel Esther on the terminus I haven't drawn the byproduct of DCC or so
just a reduced things that were going to have to reduce things to a lot of our groups let's imagine for a moment that this far boxes group is the carboxyl group on the carboxyl aghast that Dr. Bailey carboxyl like acid DEC saying Here's a diamond reagent we talk 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 reactor rights said suffice it to say so I called DCC site will Hextall sold Carbo die in bed can react with a carboxyl group give an activated carboxyl group and the structure than I'm drawing here looks awfully fancy until you think about it I'll abbreviate those like well heck sold as the structure looks awfully fancy until you think about it and then you say Wait a 2nd for the longest time he's been saying that a double bond tonight nitrogen is very similar to a double bond to oxygen so this structure this intermediate and always will you're reunite intermediate on just abbreviated as it is basically like an hydride in other words we have a car that meal with an electron withdrawing group on the oxygen and so the Amin partner which in this case I will just abbreviate as in H 2 now can
act that of course being the of the of the icbc Astor of alanine there'd or rather the bends Lester alanine alanine Denzel Esther can react I
won't take us through all of the steps of the mechanism but suffice to say the 1st step of the mechanism is the Amina nucleophile can attack the carboxyl group of the always sold urea intermediate
electrons pick up on oxygen electrons kicked down they take out what ultimately is cyclo Hextall urea rafters improved John shuffling and sell
the product of this reaction is the but plus the byproduct of dive site will Hextall radio and as I've been emphasizing in his class organic chemists a very bad about writing by-products of reactions because the typically focused on the main product product is called you dies cycle you are so
DCC by the way was the 1st 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 functional lies 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 ranches which is why Johnny and can even know they will synthesize peptides in the laboratory as part of their
research on cancer and outsiders disease never worked with the GCC are so so here we are at peptide that I
want to drive out the structure at end and talk about what can happen to this because now we have a peptide we synthesized the peptide here which are seen an interior minister are protected with protecting Europe the benzoate group on the day Leicester on me on the sea terminus the BOC Group on the terminus the BOC Group is laid by helped acid that
means that a strong acid can take off the the box protecting group and returned to you and me in technically in Amin salt they can be
deeper donated the band's 0 group is laid Bild to among other things hydrogenase also weighed about a very very strong acid like hydrogen bromide in and hydrous acidic gasses so if we take our diet peptide that we carry out Tshudy protectionist steps on a hydrogenated oil or any other .period with a tie for detested the protections that listens to you that all right this in parentheses try seat half that is a pretty strong acid is right on the cusp between weak acid strong acid not as strong as HCl not as strong as sulfuric acid PTA
is about 14 23 so it's way way stronger than regular
carboxyl aggressive due to the inductive affected the try Florida methyl group and that if we carry out a hydrogenation with palladium 1 carbon we can remove both of the protecting groups so all just remind us Allen said box is able to be removed with strong acid cheese for example FAA and the Denzel group is able to be removed by hydrogenase our sister very strong acid and as I said very very strong acid I mean for example hydrochloric
acid HCl and IOC saying hydrogen chloride in Diack said in the water column were each Peronists heated gasses alright so the overall result that this is that we have now removed both
them the protecting groups to give us just the peptides like sell in other words we have taken 1 carboxyl group came 1 amino group brought together
the other carboxyl group and the other amino group and coupled them together now I'm lying
to you just don't care about this because I haven't used a base technically will still be the TFA sold out it field the TSA sold at this point but honestly if you wanted the free basis you could just go ahead and and add a base anyway so technically still the TFA sold I wanna show 1 thing were kind of taking a traipsed through mechanism hear about sort of mechanism light getting getting kind of a summary of how things work we've taken certain mechanisms in the course of their work them over in gruesome detail like
acid Tal formation and nascent Al hydrolysis which came back to us and sugars were getting others were getting the general just it let's talk about the box the protection mechanism so
OK so here you have your BOC Group like so troops now in in strong yes said like the FAA look at probably made all the different positions in the BOC Group and the easiest way to think about taking off the the BOC Group is if we progress made on this nitrogen here so I'll write this sort of as a transient intermediate if we produce made on this nitrogen here were also set up lose deterred Carbo cat and so if we just go ahead and take out electrons gonna fragment this molecule into carbon-dioxide ,comma backside is very stable entered feral Carbo Cat Island and mean like so and then of course as I was standing at over here you're mean just on stand here with will go there ,comma indeed will probe made to give the ammonium salt by itself sorry with so I want to point out a couple of amino acids that a special we've already seen them so we saw for example with lysine and you will have an extra amino groups and we saw with glutamic acid that you have an extra carboxyl group and so in these amino acid sent in several of the other functional iced amino acids amino acids with acidic and basic and polar side chains additional protecting groups are needed In suffice it to say there's chemistry
put on these protecting groups and I wanna 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 of the
general James the things is we're going to build our peptide amino acid by amino acid starting at the scene terminus working to the Internet know the words you could imagine with the
available Al-Amin that we made if we had for example only taken off the box protecting group off of the amino terminus we could then go ahead and coupling and on another amino acid say phenylalanine L and other amino acids say phenylalanine to make a try at that time we would introduce that phenylalanine by having a BOC Group on the amino terminus on the amino group and a free carboxyl group and again in carrying out a DCC coupling reaction and so this is the type of technology that allowed the incentive in you know that to build up to synthesize the known peptide Hoxie Thompson back in the 1950's and ultimately really create the beginning of a revolution now another huge advance came along with an idea that Bruce Merrifield introduced in the 1960's 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 connects the polypeptides tool as solid support in other words to make the C terminus of the polypeptide instead of just a protecting Group a big plastic the and so let me show you the gist of modern solid base peptide synthesis and then we can run through a few with the
details so the mansion for a moment that we have a polymer beads 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 bands alcohol and that you have and all age groups on there and then there is the 1st step we couple 1 amino acid I'll call it sort of in the abstract will just call or 1 oversight change and will say that we have a protecting group on the nitrogen so this would be like a box protected amino acid and so now we have our amino acid where there protecting group I'm just calling that Fiji onto the residents and I'll abbreviate the polymer with this speedball ball here too all right now unimagined for a moment that we deeper attacked another words we carry out a reaction like the TIA reaction to remove that protecting group for example to remove the BOC 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 1st amino acid connected to the resin which I'm abbreviating as a circle no imagine for a moment that the couple in the next amino acid is so all sale coupled and will call this aura to on an amino acid again good at protecting group which I will call PGA and I think I'll move down to the blackboard here to show you what we have now got so now we have a lot to the next did and now we have our protection and imagine for a moment that we again deeper attacked inelegantly shortened things in right deep attacked step 1 of 2 couples and I'll show you what 3rd amino acid you notice that we're starting at the Sea terminus and were building up toward the end terminus all Calder's art and our structure is getting so big that I now have to go take the other black ward even at this point Barack tried peptide mineral attached and I've gone from the interim Tennessee terminates here with our 3rd residue are 2nd residue and our 1st residue and finally unimaginative in abstract we leave from the residents and we attacked all say Cleveland the protectors the sometimes don't at the the same time on the result of all of that now is that we have synthesized and tried peptide and the operation is simple once you work out the chemistry that it can be done on a machine repeating these operations 1 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 Enoksen oxytocin older peptide was a fantastic tour de force this open the job to make things trivial To make molecules of that size and 1 of the beauties of this age you really need your chemistry to work calling late and so you can use a eulogy access of reagents for equivalents of each amino acid to drive the chemistry question operate questioned why are we going from Cedar and that question is particularly profound when it is counterintuitive went on the right as
all you synthesize size it of ribosomes synthesizes the protein from and to see it turns out that there are reactions that occur if I tried to activate lets even assume I had this protecting group and I tried to to activate this carboxyl group with the CDC their reactions occur that occur that will give him a ride this serious center in chemical environments with vigorous activating agents like the DCC so you will get a mixture of dire streamers 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 with virtually no exceptions I should say we always go from cedar and the opposite of the the way of the rightness our I want to show you a couple of last chance of the genius that was involved in all of this this chemistry so 1 of the pieces of genius is really very simple it's the
polystyrene so polystyrene it is polymeric in which you have a zigzag chain of polyethylene with benzene rings attached like so you may get by polarizing the Algerian styrene them making the molecules together at 1 end of after the next after the next now styrene is Ciara from if you've ever taken of foam peanuts and put them in any organic solvent like acetone they form a big group if
you do this with a star from copy that you bring Intel Avenue personal acetone in India in there it just melts just dissolves technically so Merrifield bright idea 1 of his bright ideas was totaling linked together to chains with a little bit of guideline benzene too costly the polystyrene into a big network like so so that the trains all together and the molecule would swell up but it wouldn't dissolve and then he used that benzene ring and functional life just a few of the benzene rings on the polystyrene to put on protective amino acids which protective were so that was 1 1 real piece of genius here and so the chemistry that I've sort of been outlining here really could be thought of as right this as Fox let's safer than the 1 that we are all 1 that we could synthesize blocked all polystyrene and then we can follow with a series of the protection and coupling steps will be used to you they tried for receiving gazetted today protect the amino group and remember I said Well you're you group technically is still probated so you can add a base like Dyess approachable Nunavut triathlon leading to defrock made IPR too and 2 deep promenade the amino group that's now liberated and 3 more couple and the next amino acid and salsa Reebok C the is the abbreviation for phenylalanine Saul saved by 3 always is the CDC and now we can get part they all Fox the veil of we didn't
repeat and repeat and repeat to build up the polypeptide chain 1 amino acid after the next after the next so I will I think I think leave you with well let me let me I'll go ahead and I'll I'll
just say repeat in let's say I did this this time with alanine so again it's really we shortened and a lot of a lot of stuff here so let's say I I go ahead and do this without wanting museum so repeat and now we go but new available over the US and now if you imagine we use of very very strong acid but now we can get a peptide and if we had continued on the resident we could have gone up to testify at 5 all right the final
innovation that I want to show you what that says realize this is standing on the shoulders of giants for many years to make this chemistry possible to a point where it is now routinely possible to make peptides and small proteins so 1 of the last innovations was Merrifield initial chemistry was kind and by nasty I mean that that last step act of the protecting of getting rather cleaving from the residence getting the amino acid all off of the resin getting the polypeptide I should stay off of the residence required super super
strong acid HBR hydrogen bromide mystique acid is 1 of the reagents used as nasty stuff and libraries hydrofluoric acid and hydrous HF each through glass burns through skin burns to your bone does horrible horrible stuff insult the last innovation introduce was a businesslike about protecting Group F Mark group in the upmarket Group is a big big big aromatic unit it stands for it's in the same family as Judge Bork wrote it's a flow Reno methanol that means CH 2 oxycodone material In the Avmark group is clearly aware that base such as preparing so I'll say a milder mean base you so the aftermarket rule if you treat it with the Heerenveen "quotation mark the base can pull off of proton here take out an Al-Qaeda over here take out an oxygen alternately out carbon-dioxide so when this occurs now you end up doing the explores plus the brominated based plus the group that came from the 4 renal group which eventually reacts with some more basic plus the onto plus the amenities and so putting all of this together and I'll just show you were an example of a modern solid trainees peptide
synthesis and wrap things up so in modern peptide synthesis what's
done is the polystyrene is linked to a much more as a delayed lingering this might be a good final exam questions to go ahead and explain why this linger here is much more labile carcinogens and now you have your 1st amino acid trips alleged here and same now we go ahead now call this are 1 and so we should go ahead and with deep attacked with the news Of this abbreviated clips and then we call and as I said it typically nowadays people don't use the DCC but I will write DCC is still here's our at Mark protected 2nd amino acids are too and so now you build the old unveiled this linker here is called a widening of the tanker and start all right all along marring the PSC and finally after building and building and building your where her parenting and Salter said repeat repeat with paint and then you finally cleared with the purity and all right that is PIT into TFA which cleaves the peptide off wine later to give the peptides alright well and that no we're going to take a moment to pass around the quizzes to take 1 minute to finish up writing and then you can put away your notebook


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