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Lecture 10. Proteins and Amino Acid Conformations.

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Automatisierte Medienanalyse

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today we're going to pick up on protein structure and I we're going to be talking about where my all-time favorite topics which it is and how do you go from a sequence of amino acids to this truly beautiful structure right here is actually a good friend of mine that I spent 5 years writing my PhD about studying in doing experiments with so this is truly 1 of my all-time favorite topics that in 10 weeks that we talked to the I'm OK so that's our goal understand how proteins work and understand what the composition is an animal get a a conformational analysis amino acid confirmations and then finally looking protein structure so this week is all protein structure next week will be all protein function and in an hour or an hour scheme look at any of the questions that were going OK couple quick
announcements the chapter 5 work .period problems as usual be a couple of topics that all have you skim the synthesis of peptides for example and we're just going to skim through we just don't have enough time to talk about it in great detail but it's in the book if you order read more about it and book reports cited should be journal article reports are due this Thursday Valentine's Day and the week after that the abstracts do for your proposals case so should probably be thinking about your proposal topics now and starting use research on them and coming up with an abstract on Thursday I'll give you the format for for this abstract OK before now don't panic about this this is a single paragraph that you're going to write describing your proposal idea OK and this'll be worth 10 per cent of your own a proposal from grade so that's a really important part of this gives me a chance to give you feedback and I'll give you a format that God it's basically a formula that you could follow the 5 or 6 sentences pretty straightforward but in order to do it you do need to have your topic and I am it's almost impossible to think of a good topic the nite before it's too so you should be thinking about the topic now OK coming over the proposal topic this week and again on this journal article report is designed to help guide you toward coming up with your own ideas well OK also going to ask you today to learn the 20 amino acids the structures 1 letter three-letter codes that are more to say about that shortly OK office hours OK office hours of are going to be but today
and so on at the end the CEO of theirs today by critical and then I office hours
tomorrow by media and then in office hours Thursday and by me again and then office our Friday by Miriam came the questions about office hours office stuff and things like that OK so 1 question that I get asked a lot during office hours and that's it actually came up last week when it comes up every year is something along the lines of I have a big idea that I wanted to do something in medicine Vermont sure exactly what that is and so I wanted take a just a moment to serve talk to you about careers in chemical biology and careers in health professions OK professions broadly OK because I think this is something that we don't spend enough time talking about when it's where 99 per cent of your going to go after you graduate OK so all of
us I think everyone in this room has 1 goal which is to treat people looking at the end of the day I think all of us want the universe a better place we want to make people healthier and happier and so on Our overarching goal I'd say if everyone in this room I suspect is something like this so in the end we want to have people who are happy and that's our ultimate goal right and I suppose if anyone's really interested in making money as a way of getting to this thing you're probably in the wrong class should be taking class real estate a Order of Idaho copyright law or something like that but there's other classes on campus that can get you to the dollar signs OK so I wanna talk today about all the different ways that you can contribute towards treating patients pay which is I think the goal of most of us in this room OK so the most obvious way is to actually patients by being a medical doctor in India and I think this is what many of you have on your minds and of course and he's come up with a pharmacy will prescribe pharmaceuticals which are then given to the patients by pharmacists and again I think that this is probably the Goals of so these are all contributing in here and of course there's not Tom interests there's idea those which are also participating in there is knows just other other types of dentists all of these are sort of the hands-on ways that that we think of what we think about treating patients over here here but from what I wanna talk to better although other ways that you can contribute to this ultimate goal and that don't involve say going to medical school don't all us and you know becoming a dentist or something like that I think you are all aware of what it means to become a dentist and you know what it means to be coming up ,comma trips OK but ultimately someone has to come up with the drugs the pharmaceuticals the therapeutic that the pharmacists are going to put in there going to promises are going to put in bottles and other entities are going to prescribe and so and before you can get to this stage over here there's a whole series of clinical trials that take place OK so the clinical trials are staged into 4 stages when the 1st stages looking at toxicity and the 4 stages looking at dosage in every state is looking at efficacy which is to say effectiveness case so someone has to do those clinical trials and the people doing these clinical trials are on our side and these clinical trials and include scientists so Ph.D. is but also and and these are running these as well and these are thinking about what dosage to use and pharmacologist play a role as well in designing these trials looking at side-effects and interpreting data gain on the PhD side of things and there's PhD's were analyzing data who are thinking about side effects who were thinking about all kinds of aspects of the trial they're thinking about and the other data that would say DNA sequencing data at a trial evolves from a particular mutation of the cancer associated protein so what has to be thinking about the underlying biology the underlying chemistry involved and so on this is 1 role that does students from my laboratory place I have since my laboratory designed clinical trials you graduated from my lad who have Ph.D. is in chemical biology and are now designing clinical trials in interpreting the data OK so now in order to get the drug to the clinical trials it turns out it's a long process it takes about 10 years or so to get a drug into a clinical trial and so I'm kind of at the very beginning of all this and the other was a series of experiments are done and over here by biologists and chemical biologists can goal here is to identify potential on targets that would be useful in organisms in humans OK and might not start with humans might start say that of zebrafish where maybe you identify a particular mutation that causes heart muscles to grow back and see professions superficial this clear organism that you can actually look in and see their hearts a said subdued if you have the took flight something else so somewhere else to go about it OK so alive so someone has to do that someone has to get foot in the door and identify and what what the ultimate target is going to be that this cancer thing that's going to target case of this again is done by I'm biologist chemical biologists and on these at all levels so you tomorrow can go out and when you graduate from UCI you can participate in this sector of the level of a Bachelor science you can have a master's you can have a Ph.D. all of these give you a way of identifying targets OK so ID targets now wants the target isn't isn't here and then someone has to chemically synthesized the drugs right so 1 has to synthesize the initial leads better than going to eventually become the therapeutics come and so this is typically done by medicinal chemists so medicinal chemist but also this is done by Camby chemical biologists to devise assays looking at how effective the compounds are computational chemist play a key role so someone has the model whether or not the pharmaceutical are actually targeting the drugs as expected and in doing so they can start to decide whether or not they're getting more effective compounds they can use this compounds that buying worked actively to target and avoid side effects and so this again is done by people who have agrees MS degrees and PhD's OK so let me just talk very briefly about this so the the if you went out tomorrow got a job at say Genentech as a BS chemists Justice CBS chemical biologists worked in a department protein engineering at Genentech which you would be doing is you working as part of a team to synthesize compounds perhaps if you work in medicinal chemistry team or appearance protein engineering you'd be synthesizing proteins you'd be testing proteins you'd be trying to engage the efficacy of those things and trying to decide whether or not things are working a pay and on your role on this team is the kind of like the the foot soldiers Acadia here the muscle that makes it possible to do the science of paying out the thing is if you're working on a really good company and you're doing amazing science eventually you can get promoted up the ranks to be at the same level as a Ph.D. scientists say so when I was a Genentech I had a friend who never got a Ph.D. but he published 7 papers in Science when he was there and they took that as the equivalent of a PhD and he was promoted to levels of scientists which are usually reserved for people of PhD's the pH these are running the team's that typically running teams of about 4 people and other people on those teams include a couple of PS level people at a 181 masters the Masters person is kind of like a super technician whose Konerko Rowling the resources directing things are helping things along pushing things more quickly
and that type of thing but sometimes recalled Research Associates but it's the same sort of idea OK so I'm in here but so there's lots of opportunities in here and then eventually someone has to devise to do things like test the compounds in an animal models and then also synthesize enough for the ,comma compounds before you get to clinical trials and so actually I'm missing an important step over here and I think what I'll do it's all have less so will call the scale of case so has to scale up the compounds and the scale up is typically done by process chemists case so if you're that person who loves organic chemistry analogs mechanisms This is for you apparently basically I'm really understanding the details of a particular reaction and trying to improve its yield city can get about 10 kilograms of stuff enough to write a thousand person trial or something like that OK so someone has to do the same again and this includes us some BS level people but also analysts and also Ph.D. I haven't talked very much about the MS MS is a good thing if you don't plan to go on to serve a leadership role on the team if you're totally happy at having been at the intermediate level a masters of science gives you a higher salary and over the course of a 30 year career and a difference at 10 thousand dollars a year comes out a lot of money apparently especially of compound apparent so this gives you just a little bit of more of freedom but not a lot of freedom really that the most sort of creativity and freedom is at the level of PhD until you burn it if you're at this BS MS level 3 just being successful OK so anyway in the and this leads them to the compounds which then can be tested in the colorful trials which ultimately leads over here to the happy patients OK so on a couple of thoughts about this so I have a diversity of students in this classroom and 1 guy over there he text messages through every class address me crazy it doesn't even seem to listen to me at all but I also have some people who have 4 0 GPA it's a case I have a wide range of other students in a class like this and I have a message for everyone no matter what your GPA is no matter how well you're doing here at UC Irvine matter for text messaging through every class at UC Irvine and there's a place for you in this mutually challenging enterprise to be a disease like cancer we need everyone obtain it's not true that just the 4 of those get to go on and on go on eventually to win Nobel Prizes there is a role for everybody and I've seen people with 2 3 GPA is coming out of college who have gone on to win presidential awards for the quality of the science and that's 1 of the cool things about science is it's a total Myrick driven enterprise so if you were really good and you work really hard and you bring a lot of heart and you put away your cellphone a key moments of you to have a role for this effect and so let me talk to you very briefly if you want to be over here and on your GPA doesn't let you do that a case of 1st if you're applying to medical school you should be thinking about having like a 3 6 are higher GPA I've had trouble getting students as medical schools with 3 it's it's that unpredictable the indicates the should be having like a 395 GPA pay and I like Ph.D. graduate school he should probably have some in order 3 3 2 3 5 minimum OK now don't panic if your GPA is below that there is a place for you and I want to talk to you very briefly about how to get their case of number 1 is you can start at these various levels positions in a company and as years go by your GPA from the undergraduate becomes increasingly less important if you're at this company and you're doing really good science and on your oppressing people there and you know that calculus class that she got a C-minus and that's been bogging down your career suddenly becomes a lot less important OK so every year that goes by your GPA gets less important to attend then at that point that it's all about heart and your ability to rise to the occasion which is good it's now the other thing is if you want to get goes straight toward a PhD and you don't have said that you know 3 6 A 3 8 GPA don't panic either which you could do is you can go off and get a master's degree at Cal State and then come back to get a PhD at 1 of the top universities in the country I would suggest that you don't go down onto a low-quality institution for getting a Ph.D. type and this is not a leaders of a pay you can look at my own record of obviously I have a lot of vested and high-quality universities but from the point is is that we actually have something like 200 chemistry PhD granting universities in the United States of those of most of employment for the kind of top-level jobs in both industry and academia are coming out of probably 50 to 60 of them peso you drop down to say you know a third-tier 4th year PhD you can get a PhD but on its economy hard then for you to come back so a better way to do it would be getting a master's degree at at Cal State Fullerton Cal State alike are outstanding institutions you get your masters from there and you show that despite you know that that calculus he still lots so when we should take a bet on and then you come back and get a PhD at Canada UC Berkeley or the CLA war or Harvard or jobs Hopkins or any of the great institutions here in the United States were made you go abroad and get a PhD from Cambridge for and you know 1 of the good schools in Australia water and so on and so forth OK so there is a will there is a role for you at whatever level you want to participate in this major enterprise of treating patients and the real question that I want to challenge U.S. is what you want to do argue the kind of person who likes to think about molecules at the at Adams in bonds level in which case then you probably want to be somewhere over here if you're the kind of person who likes customer service and likes you know having patience and coughing on you and I know you don't mind blood and stuff like that you probably won't be over here Casey basically get dial-in whatever level of interest is ultimately yours a and no matter what you're courage EPA is there is some room for you pay the questions about them it's again this comes up every year during office hours and this year I thought I'd make a more systematic and just tell everyone to questions OK from 0 you know 1 last thought none of this is set in stone you know the great thing about the United States is that you can reinvent yourself I'm so if you end up going to dentistry school and you don't like it change the path had friends actually have a friend who got a master's in on computer science and was a programmer and he hated it the athlete hated it so he went back and got a degree dentistry is now a really happy densest affair so no matter what you're doing you don't necessarily have to get locked into 1 thing there's considerable room to reinvent yourself and then you static earlier experience to be more successful at your next career OK so that's 1 of the great things about this and that's 1 of the things I really prize about our system OK questions OK well stuff here I
want to move on and I would talk about proteins next and specifically I want to talk to you today about protein structure before I do I need to review from what we talked about last nite so last time I was telling you about on and how on Oregon
had a diversity of different structures and what we saw last time when is mechanisms of RNA polymerase we saw this last week ,comma but our message on Thursday that what was after the synthesis of the of the of modern-day heavy modification takes place we saw that both ends of the mark on a modern-day far from capped the altered the splicing events there's cutting and pasting that takes place after the messenger RNA supersized for that matter after synthesis of RNA the other covalent modifications that are taking place on the foreign aid and we saw an example of that being out transforming a tiara better sit beside that and have trained that have modifications to their rear bases those modifications as we saw how important functional consequences in terms of determining the specificity of the amino acid that's appended to the 3 prime and of the T R a day OK we talked a little bit about that and how amino Wieseltier already said that today's Shiite reads those types of modifications out it reads out the intercut on and on and on the cracked amino acid is appended to the crack to urinate on it as we saw is also a very versatile biopolymer beyond its ability to be both of them on and also a two-yard and for example we saw catalysis by Faraday and this was catalysis by a class of party based catalyst that we could now call right designs and it turns out this actually works very very well and we also talked a little bit about binding activity from Nantes by an act of mercy and so all these things make already the versatile molecule that is really right round for all kinds of Discovery's whenever I pick up signs and nature there's something new about our day in their ends up and you know the chapter that I had you read has large sections of it that are changing their being cheap transformed overnight but by discoveries that are being made in laboratories here use your vine and here at other universities across the world so this is a really exciting area to investigate it's an area that I really occurred you think more about because an artist so versatile that it continually surprises us
OK let's talk about protein so we're continuing our journey down the central dogma of molecular biology we talked about DNA we talked about art and were now I proteins and other proteins are made proteins because there they were thought originally to be of central importance the cell they still are essential portends despite everything I told you about of RNA and DNA and showing 1 of my own little world diocese but on here's a here's a great picture of Max fruits on the left and I'm John can drew on the right and then entire who shared the Nobel Prize in 1962 for determining of the 1st three-dimensional structures of proteins and back in the early days of the Structural Biology they would build a little wire free models of protein sources before computational modeling was available and so and there is actually a tremendous craft involved with building protein structures and result of this tactile feel as you have these things in your hands and we still have a little bit of that Structural Biology nowadays we use 3 D printing but it's the same idea and so we like to think about things in 3 dimensions and 1 of the things that always entranced me about this topic is that of Burgundy taking things off of the flatland and talking about them in 3 dimensions OK so the
1st thing I'd like to ask you to do it is memorize the structures of the 20 amino acids and other abbreviations that the 3 letter and the 1 letter codes here depicting just the three-letter codes are just the 1 letter codes and the amino acids be roughly grouped according to the functionality to the side chains so at the very top here are some side chains that 100 Bilic including acidic what's functionalities like on despotic acid which has the abbreviation D glutamic acid and abbreviation but also the hydrogen bond owner tyrosine but here are some aromatic amino acids with mere aromatic side chains and then some basic side chains please do this as soon as possible and starting on Thursday and is going to assume that had that I could talk about these without kind of referring back to the histidine has a submitters all functionality trip but there has it all functionality so and start memorizing this right away because that will really help your understanding of what's going on and in addition there are other functionalities they're fully hydrophobic bodies of aliphatic functionality all aliphatic amino acids shown here
OK and then on the last of our 20 but there some that contain sulfur this includes methionine and sustain them and then some other ones that are hydrogen-bonding polar amino acids and some of these 2 of these in fact have a 2nd serious center at the beta carbon notice that we're going to be calling the carbon cuts Alpha to the Carbondale we're going to call that the Albert carbon and then if you go out but to date the 2nd carbon away it's called the bit of carbon and 380 has a 2nd stereo center at this bit carbon I didn't
up pointed out but the other amino acid that has a 2nd serious and bitter carbon is Isa Lucien OK so I solution has an S serious center in the commentary log in gold rules for assigning S and or stereo chemistry and 389 has an aura serious center in opposition those to you just have to memorize there's no way around it OK but good news for all over the other I 19 of the 20 amino acids this serious center at the Alpha ,comma is fast OK so every single 1 of these hasn't as serious and at this alpha carbon the 1 exception is glycine which does not have a stereo center at its Alpha carbon expense OK I expect that you might have seen this in binding 9 or something like that if not don't panic just go ahead and memorize the use of them as quickly as possible said the questions are bottom OK so
when we refer to the amino acids what are convention in this class in the convention and been biochemistry compiled is that we're going to refer to them using the 1 letter letter codes followed by a number that number designates the position of this residue residue is another way of saying amino acids within the larger protein OK so if you had said a protein that has 180 amino acids and at the end the that position 171 the amino acid cited the amino acid was a histidine you would designate this as page 171 OK and so on and obviously this is a manganese iron and so it's just going to get the regular elemental designation OK so anyway that's a dementia want to follow and pretty straightforward OK so here's
what I want to do over the next couple of days I want to understand the forces that I take a set of amino acids like when I showed up the previous 2 slides are our you know to slides back on and then understand how these amino acids forced the protein to adopt a particular shape pay because the sequence of amino acids that encodes a protein In turn specifies 1 predominant shape can this is actually kind of a creator of pretty wild concept if you stop and think about it but again and if you have a particular sequence of amino acid that in turn will dictate 1 particular shape OK and there are some the proteins that refuse to have any particular shape their they're largely disordered and there's a kind of a special exceptions so for this class where words come about a foundational level rolling and talking about proteins that adopt 1 predominant shape and if you start to look at things were closely there are a lot of exceptions but we're not going to worry about the effect so again articles understand how you go from this to something like that so I understand the forces
behind protein structure OK so the 1st thing we have to talk about is what happens when you string together the amino acids so 1st of all the the backbone of the peptide or protein has some direction ality associated with that and 0 by the way I'm going to use the words peptides and proteins interchangeably but they're not OK so peptides are a short sequences of amino acids that are connected together by bonds and in turn these are so short that they don't adopt any 1 fold or 1 particular structure of proteins are long enough so that the amino acids forced the beep peptide by a polymer into a single confirmation of case so it takes a certain minimum length short peptides that have say 20 amino acids or less are typically so largely disorder when we put them in a March too we see all kinds of things OK there's all kinds of different conformations and these things are just kind of flying all over the place if we make the on the protein longer if we add amino acids on oftentimes we can get to something it's more structure at least stuff especially were barred from sequences that are known to be structured OK so now and we have to talk about and according to that convention in designating the sequences of peptides and proteins were always going to list the the but worries going to list the sequences in order from and terminus on the left to see terminus on the right to notice that the C terminus is the carboxyl carboxyl and of the amino acid so in each case of these amino acids over here we're going to have the carbon yield or the carboxyl late on the right and the Amin and on the left hand something that's really important is the sequence these sequences that go from and to see that cannot be reversed without resulting in a different peptide sequence the 2 sequences the 1 on the top and the 1 on the bottom are constitutional isomers of each other they're not a dire scary murders there nothing more than just by summer's end on the way he can tell is notice that the positions of the carbon heels and ages are all wrong between these 2 OK in fact it's very likely at these 2 will have different binding profiles and it's very likely that these 2 are going to have say different flavors if were looking at a peptide that had a sweet taste for example because of the arrangement of the carbon heels arrangement of managers and will really determine hydrogen bonding to the backbone of the peptide and I typically say a taste receptor for talking about Sweden's a taste receptor will sanction bond donors and acceptors that will interrogate that backbone and want to certain arrangement of not backbone and the wrong 1 the wrong isomer is likely not to bind to the target I'm using the word likely because of molecular recognition is very hard to predict but is very likely that it's not going to buy case of these 2 molecules are different and that's why we have to have the convention there were always want to write these with the N terminus on the left and the C terminus on the rights of notice here that I not listing the and terminus and the C terminus it's kind of like when we talked about DNA sequences we had a fight crime and then the 3 primary and but oftentimes we didn't last of the 5 crime or the 3 prime right we just assumed that they were there so similarly with amino acids sometimes people ride H 2 and not on this side and C 2 wait on the side but remembers a time actually people just leave it out of its kind of understood in terms of always from last Zeidan was always on the right hand OK so on that's the dimension of going to follow and here's something else that's extremely useful for you to know and to the point where I had attempted to ask you to memorize it and which of these PK is I had asked you memorize like case if future 51 C with me working a year earlier courses with me but these actually are very useful and undertaking is that you need to memorize all shown here and you don't have to memorize them to the nearest decimal place just round them up OK so just come up with something that's roughly equivalent so what I mean by that is just know that these carboxyl late side chains of blood PK is on the order of fortified herself somewhere in that range and the reason why the exact numbers are not so important is that the environment that the functionality finds itself in Cantua manically alter the PKK and this is a property that proteins are notorious for taking advantage of you can have for example of carboxyl casted site that's our positioned in a way that makes it much more acidic than the PKK that's written behind the might suggest a pace of proteins will will tailor the environment that these functional groups are going to be founded and in doing so drastically alter at times the the case of the functionalities so I want you to have just the range of the PKK has in mind you should know for example that when a peptide like this 1 is dumped in pits and water which is obviously the Nunavut pitch 7 being neutral and here's what we would expect a K we'd expect to see these carboxyl leads the protonated we'd expect this tyrosine to be protonated it's only . 3 1 3 per cent of the protonated at this time that this decay at this pH etc. OK so this seemed terminus of it's going to be the protonated the end terminus will be protonated as this pH and Jesus I realize the wrote this last year but it's kind of trip OK when I think about the year when I think about proteins 1st thing that comes to mind a charge functionalities charge functionalities control lot of the ability of the protein to catalyze things to bind to different things so the 1st thing that you actually need to know the is on what is a charge paid any kind need to build a predict that quickly OK so I'd like you again to memorize these the case just the range of had not exact numbers which just the rich
OK so the side chains are going to dictate the SSI genes interact with each other and that in turn is going to dictate the folding of the protein cases goes back to the major challenge that I set up earlier had we go from amino acids to this complicated three-dimensional structure what we find is that the side chains are going to be packing against each other and that in turn is going to largely dictate particular folds of a protein OK and on the evidence of this to be found in the fact that the trends in society site interactions on nearer the strength these interactions OK so the on side chains side-chain interactions found most frequently are also the ones that are the strongest a case of for example at the very top over here we have phenylalanine binding to phenylalanine this is user to amino acids that have Denzel functionalities these Benthall functionalities large aromatic fennel grips can pack against each other quite readily and so for this reason on this side chain is on highly enriched when we look at but when we look at it and serve statistical analysis of sight she's found structures a case is a very strong interaction and is therefore on used quite a bit by proteins to set their structures on the other hand the weak interactions this is 1 that involves the amino acid glycine and these are very rare a case of lysine doesn't have a side glycine is the 1 amino acid that had no serious center it has 2 hydrogen is added Alpha carbon and this 1 does not form good interactions with the other side chains and so for this reason on its interactions with other amino acids very rare and its interactions very weak it makes sense OK and so let's
talk a little bit about about the specifics of those interactions from 1 side chain to another what we find when we look at this time is that the the strongest ones are most common that's the point of the previous slide and the strongest ones typical things like aromatic functionalities blinding to aromatic functionalities and know that I'm showing this as an edge to face interaction that's a very common mode for side chains they interact with each other on another way is through a dispersed of course this was that the walls interaction that I introduced you back in Chapter 2 and again these are common because they provide a lot of binding energy and this from the start a binding energy can be used to drive protein folding less common and perhaps more support perhaps surprisingly so are the ones that are more predictable OK so you you can readily predict a charge charge interaction on say the surface of the protein but on it turns out is a relatively weak in Juneau y so why these weak interactions charge charge interaction Is it depends on pH yes yes I heard a couple people say a clear sir in water and in these big Reiser in water environments oftentimes there's counter ions which can partially shield these charged these charge functionalities or the water itself is competing for hydrogen bonding to these charge functionalities and that has the effect of weakening the charge lessening the charge and making these charge charge interactions much weaker than they might otherwise be expected to to be and so many show you 1 example list of this primary in functionality it would be up and down on a lysine side chain and other nearby chloride ions from sodium chloride could readily interact with this primary if it's the chloride is interacting very closely that's going to partially neutralizes positive charge right claw is negative and the positive charges positive the to a visiting neutral and so the net effect is that this interaction is much weaker than it would otherwise be bound over here the hydrogen-bonding ones are also unexpectedly weak and again that's because they're going to be competing of water water is the ultimate hydrogen-bond donor and accepted and it's capable of readily forming Hajime bonds and this has the effect of weakening designed in hydrogen bonds in ways that are very bad day care if you're medicinal chemist somewhere and you design the perfect Taejeon bond you might be shocked to find that your only gaining say are you now have a cake mole of binding energy which is very aggravating as you might have done a lot of work to install that hydrogen bomb OK let's take
a closer look at the 2 proteins that bind to each other and when I'm showing you is 1 half of a protein-protein interactions at the top of this is on protein 1 and in related down here this is protein too of coloring and Adams according to their identity so for example on oxygen is colored here in red wine Nigerian blue and sulfur in yellow OK I notice that the interface of the prior to the 2nd protein-protein too is dominated by hydrophobic functionalities OK there's a lot of communism hydrogen is down here there's no I'm Hager filet functionalities carboxyl awaits hydrogen-bond donated donating carboxyl Ahmed's etc. It's almost entirely hydrophobic stuff said the interfaces between a receptor is lying in the big entered the big money in terms of the interaction energy is dominated by these aliphatic were aromatic functionality and they're the ones that are dominating down here up here at the interface with water on the outside of a protein or an outsider protein-protein interactions there's on lots of charging that it charge functionalities such as this carboxyl side chain from a glutamic acid this Amin functionality and there's lots of pages Bilic functionalities that can interact with the water this has the effect of orienting the protein in this interface between 1 protein and water makes sense she makes sense right and we also alluded to this earlier the quarter when we talked about the hot spot a binding energy we talked about non-covalent interactions so this is kind of a concept that we've seen a couple of times now OK I want to talk to you
next about peptide structures and why peptides yourself and they will get onto protein OK so here's a up into about a cold US cyclists foreign this is actually given to a transplant patients patients who have had liver transplants other types of transplants as a way of suppressing their immune system it's an immunosuppressant on notably this is kind of a big exception amongst peptides because it can be given orally at a meeting did you give it to someone in pill form and as they can they can take it that way and I should note that in the United States culturally we prefer pills that are given are we prefer to give pharmaceuticals in pill form but that's not true in other countries other countries prefer things like sub Lingle suppositories etc. That is what Salazar giving pharmaceuticals in this country that we prefer to develop drugs that can be given in pill form correlate the problem low is that when you give someone a pill it flops into the stomach where there's all kinds of producers to hide relies on the bonds OK so if you give them a peptide that unstructured those producers but will catalyze the hydrolysis of the armored bonds OK and that in turn will come result in the destruction of pharmaceutical making it in effect right at the pharmaceutical gets digested up readily it's not going news source of drug maybe it's a good amino acid supplements but is not useful as a therapeutic and so on but can be exceptions this are peptides better cycle lies a notice that this does not have any free port In Aussie Terminal the N and C Terminal II of this peptide has been hidden away as the peptide has been made into a take it's entirely ring-shaped certain cycle was turns out this is fairly general bid you can take peptides and connect up there and see termite if we're close to each other in space and in doing so make the peptide highly resistant to being chewed apart by the and pet today's by the producers found in the stomach is actually works pretty well this year's very commonly in drug development and some other little things about this that happen to make it even more resistant are on notice that each 1 of these and nitrogen so our .period modulate with this exception over here in this 1 and these are largely methylated will line here that indicates a methyl functionality that in turn also makes it very hard for for the producers digest and the bonds of US cyclist Florida so this is really a major exception the other thing is that these the loss of these NHS turns this al-Ahmed into being something that's largely hide filet into something that's a little bit more hydrophobic and this helps a peptide slip through the membranes that are found on the surface of the cell OK the those plasma membranes the OK and so let's talk a little bit about what you can do with peptides peptide of binders to a particular targets relatively easy discover as many sources of the and some sources we did talked about you can use stage display you can use a variant of actor murders player messenger RNA display but you can also search through organisms found on the planets like this pit viper shown here and identify of venom peptides in the pit viper so this peptide works on by binding to a particular after active site OK so you down if you could solve the structure of this bound active-site or do a lot of on structure activity relationship studies where you mutate eat these on-site chains that identified one-half of the peptide that's working you can make an analog to the original starting peptide ability explain that a little bit so that the pit viper somehow and I don't know how but to do this part of the area carefully you collect the venom OK and then you start looking at various fractions of the venom to identify the active ingredient that's making an effective as a on I think in this case is that of entire inflammatory pain suppressing peptide see you look through that you identify its active peptide which happens to be this long peptide over here you then make a bunch of versions of this long peptide that a shorter a case you make 1 that has the 5 amino acids at the C-terminal as 1 that has the 5 amino acids at the end terminus any test each 1 of us here this is some work there but it's not so hot it's pretty easy to synthesize peptides of the book provides more details on that OK so if you do that you will eventually find that you don't need this big long peptide instead you can get away With just a shorter analog peptide and then if you and if you spend a little bit more time unless you might find some amino acid substitutions that make it more effective so replacing for example this ring like the losses side-chain correlating with in this case colony case you're making a little bit simpler lowering the molecular weight next step here is to do make analogs of this list of the peptide over here and try to find a simpler and avert variant of it OK said you go down here to the simpler variants and then this thing it turns out is not so orally available but if you make a dispersion over here this actually is orally available because cancer drug cases this is actually a the of prescribed pharmaceutical and this actually survives in the in the stomach faces even has enamored born it's not getting chewed apart by peptides by praises its surviving in the
property is rich environment of the stomach case all of this stuff over here this is what I was talking about earlier today when I was talking about all the stuff that medicinal chemistry going these chemical ballast because that's the stuff that we do a parent start some large peptide peptide we try to cut it down and then I tried a I take it and turn it into something it's orally available and is typically this is done in teams of like 20 to 100 people working on a project like this Hi this is not done by 1 sole person who you know kind of makes it their mission in life too work workout this details typically that person would be part of a team with the computational chemist structural biologists and chemical biologists to do the assays of medicinal chemists supersize easing its ability as a big team effort to get to hear and then this compound over here might sell it you know hundreds of millions of dollars if not billions of dollars a year in I'm in sales 10 OK so let's talk very briefly about the synthesis aspect of this this is ongoing to be show you after this summer like you to review this very briefly this topic and and then skim through the book fair so here's what I would like you to know and this is essential knowledge of what I would like you to know is that if you mix together 2 amino acids in a high concentration that will happen is you'll get an exchange where the Amin functionality of the 1 amino acid and the carboxyl at Cilic acid functionality of the other amino acid will exchange protons it's a case of the proton on the carboxyl gasses will protein acres and give you ammonium ion and then also a carboxyl late please let exchange happens very very rapidly yeah but Nilo mn bond results you can mix these 2 together for million years nothing will happen furthermore you could he please up for a very long time and yet you get a little bit of avid bond coming out but you'll largely get a lot of other junk as well OK get all kinds of side effects side products when you start heating things up the high-temperature case so instead of what we do in laboratory is I use some sort of carboxyl 8 activation reagent this is analogous to the tea on day therefore that activated Esther the new noise ulterior that I showed last week that activates the amino acid this is analogous to that on the way we do this is to use activation region that's typically a ,comma Diamond OK this is that this is an ICE approval variant of the dice cycle Hextall ,comma diamond that you learned about back in 1051 C said this is the equivalent of DCC remember DCC it's like OK so this thing is a on fantastic of electric it's even better electrify all if it's protonated carry this then acts as electric file to be attacked by the nucleophilic carboxyl way to give you this entity intermediate which is a I'm a ISO urea OK this is all so urea and is now an activated carbon deal OK so this is all Nissley teed off to form avid bond because you've turned this oxygen adjacent to the Carbondale into the world's greatest leaving Group take key steps this means that when you get when you add the median you can then readily form did you can have any attack this problem electrons get kicked up here electrons come back down kicking off a good leading groups and that leading group that decades kicked off is the urea notice that this gives you a carbon-oxygen double bond which as he talked about is very strong prices goes back to what we talked about the Tamas Ajan of the DNA bases and I point out the strength of a carbon-oxygen double double-blind here we see it strike again that strength is key to understanding how this reaction works it also helps if in the case of DCC that urea precipitates out of solution from having the reaction the lowered by the shanties principle because in this case that 1 this diets of purple urea not so insoluble take a and by the way for the aficionados an audience if you're wondering why Reno and using dice approval ,comma limit but oftentimes we switched to the diet from the cycle had sold to the diets of pro ball because chemists that spend a lot of time doing these reactions and uh believe me that you end up spending a lot of time doing this stuff when you spend a lot of time doing this stuff of small quantities of DCC that get on your in your skin turned into a potent allergen OK so this will also react with carboxyl Carson's found on the surfaces of the the proteins found in yourselves and I on your skin and and turn that will lead to a massive immune reactions so what we do is we switch around between the last dies cycle Hextall variant the Diet's approval variant and we also try to be extremely extremely meticulous about not inhaling the stuff about not allowing it to contact her skin etc. That is really really essential this stuff is really nasty the pay and you know I have friends who can even go into certain laboratories because that sensitized to the use of this kept this this type of chemical OK so this is the level of detail that I would like you to know but understand peptide synthesis of Texas provides a whole lot more the level of detail and I think she just a kind of skim through it in on stress about just skim through it and but I'd like to know this particular reaction this 1 is useful but this is this is the reaction that I've done a lot better I think almost everyone you can buy wasn't he has used many many times OK so
after the on peptide is the size and how are you going to get to a larger protein cake to waste way number 1 is to coax bacteria sales to synthesize a large protein directly for you OK we talked about that in the context I believe this is Week 1 where we talked about the call acting as little factories to synthesize proteins for you OK so that's 1 way to do it a 2nd way is to stitch together a bunch of short peptides and aunt in doing this then you get to a much longer peptide that eventually becomes its own protein it turns out that's actually kind a nontrivial on each 1 of the peptides has functionalities dangling off the side chains etc. and so it's not as easy to do that kind of thing as of a woman like so instead of we've we've invented a series of reactions that allow us to do this kind of convergence synthesis to make a larger protein and on the way this works here is 1 example of this is 1 of the colony of chemical ligation discovered by us the cat and here's where this works you have a fire Wester at the C-terminal said this would be the carboxyl instead of a hydroxide over here there's a sulfur and then in ah ah could be something like a fennel functionality cases that's called a thiol ester this happens to be even more reactive than the regular esters OK we know investors a reactive because we saw an example of that with the Amin always maturities which were estimates yeah right OK so we start with this very reactive functionality and this can do something called a transistor fication 4th fire Wester an exchange where this s aura of functionality is kicked off this violate functionalities kicked off to give us a brief an intern assisting side chain the sulfur of existing side-chain nucleophilic clear attacks this Carbondale 1 upon doing this well part of it is driven by the tremendous nuclear felicity of sulfur sulfur is the king of nuclear Felicity it loves being a nucleophile part of that is if we look over here at the periodic table OK so sulfur is 1 Roble low-oxygen but these electrons are a little bit further away From the nucleus and being a little bit further away they can be more readily given up they can be there a little bit further out of orbit so they're more effective as a nucleophile so again on sulfur the champion of nuclear Felicity was going down the periodic table selenium is even better tourism oxidizer so quickly we don't even see a selenium those even better over but sofas are grand champion at least income 128 OK so sulfur attacks this month activated fire last that in turn gives us this intermediate and on this intermediate can then do a attack where this being the lone pair city attacks the Carbondale giving you a thus giving us are taking electrons out oxygen which in turn collapsed down and in turn give us a new element bond and moving off the sofa of the Sistine all chain look right now why is this useful this is useful because it gives you away of stitching together to big peptides K peptide 1 over here as indicated by this little squiggle that could have 20 amino acids going off to the left to imagine 20 million acids going this way peptide too again indicated by little squiggle 20 amino acids going this way and here's the thing if you mix these 2 together and you will get it in bond out of it but uncontrolled is that you know without even thinking about it all you have to do is mix the 2 together maybe control the pH of little Peach buffer and then you get on the bonds out of that it works that well OK so that gives us a way than and of taking 21 over here 21 over here putting together and you get 42 if you do that couple were times you're talking about really big assemblies of proteins This is how you could synthesize really big structures structures that I'm stock has real consequences for your experiments this virtually Welch usury commonly it's often used to incorporate unnatural amino acids a little bit different than that the suppression technology that we talked about in the context of RNA but in this case you just chemically synthesized whatever you want including unnatural amino acids including weird backbones said that I'm not talking about today chemistry this
elegant must have a natural analog and it turns out that when we look closely at selves we find that cells can also do a self splicing reaction where proteins newly synthesized by the ribosomes will actually cut and paste themselves apart without any intervention from other proteins OK so no other catalysis that's available here's the latest works so on some proteins and synthesized by the ribosome here's and terminus here's the C terminus and 1 by a mechanism that offshore in the next slide called protein splicing and inserting intermediate between 2 Eckstein is cut out is actually you know physically removed this is analogous to the introns of the messenger RNA right we talked about splicing of messenger RNA I'm here were saying something analogous to this that instead of having already back this has the protein that backbone and again but this also something happens spontaneously on so you synthesizers saying it put it in water and before you know it in team has dropped out when we take a look around the mechanism recalls what I showed on the previous slide that call made of chemical ligation involves a similar rearrangement of the some of the backbone of the pretty OK
so let's say protein supplies derivatives years works flanking on the N terminus of the teen there's always assisting functionality that gives us the wonderful nucleophile Of that violate functionality of since the peso this violated now attack the backbone of the Of the XT when that happens you get this intermediate structure and then by an end to St sold transfer this other flanking Sistine can attack this fire west of this is this is kind of like I ,comma reminds you of like Trekkies artist OK we're going to basically be passing off and activated carboxyl carbon deal were passing off from 1 person to another to another etc. it's a high-wire act but OK so the fact is that this is the fire Lester exchange this is analogous to the
1st step of and the need of chemical ligation I showed you have very analogous fire Lester exchange reaction
case so again by research change over here that has the effect of bringing these 2 x stands next to each other and in the final steps they asparagine functionality the side chain of asparagine functionality attacks the carbon yield back the debate freeing up the interior down here and give you this image functionality take and notice now that the backbone has been restored the 2 x are bound to each other covalently through bonds of this works really well with and it's actually found naturally occurring in something like 300 different proteins in various organisms in fact that New England by has a whole website that's dedicated to tracking these so if you're interested in can what this up on Google and you can find a a big was staying in all kinds of examples in order for this work to work however there is conserved sequence this isn't gonna work with just any but protein had this really requires for example the Sistine at the I N terminus of the interior and another associate at the terminus in and this asparagine right here furthermore the team has to bring the 2 hands ,comma close to each other right if the interior is set out the 2 ends can find each other then structurally this cannot happen right if the answer not no wander around nearby no reaction as possible so big for these reasons and we find lots of concerns sequences with Indian teens and certainly the oldest all the amino acids that I've depicted on the slide because that's it's mechanism they make sense questions about anything we've seen so far OK in that case on Woodstock next about conformational analysis but when we look at proteins we find that they're not just flopping all over the place mn bonds for example which hold together proteins occupy only a small amount of a sequence of three-dimensional space that there's really limits on a rotational angles within the protein and this topic we're going to call conformational analysis and we're gonna look at it in some detail over the next 15 minutes and then on the next lecture will cover in much greater detail a so that's the plan I want to talk to you about how to look at structures and to bedecked the predominant confirmation I'm not going to call it the 1 and only 1 confirmation because in fact what we find is kind of a bill prove confirmations this is shunned by this upper graph over here so this is a histogram meaning that a higher numbers over here are higher on this Y axis over here or z axis over here means more representation and others that there is a predominant pig but there is some population that exists in these other otherwise flawed and rotation angles work defines invitation angles down here so yeah there's going to be some dominance of 1 particular confirmation but for the most part of there is also some other rotations are possible but the goal again those for you to be able to predict what that dominant confirmation is going to be and it turns out that actually just using exactly what you earned back in software again chemistry you can make predictions about what the Manassas items and a like and that in turn we can start to understand how proteins can fold into particular confirmation OK that's a goal let's talk 1st about
the hydrogen bond OK start basic it turns out that pension bonds are not flying all over the place and this is said by the fact that the hydrogen bond accepted by the Louvre in Paris on oxygen which look like these Mickey Mouse ears because Abkhazia's oxygen here's the orbitals encompass these 2 Lund pairs notice that they're not going all over the place there like Mickey Mouse ears they have only 1 particular orbitals that are to your bottles that are involved appear the electrons accounting confined to those bills that not gone all over the place and so for this reason I what we look at hydrogen bonds to this oxygen we find that behind tree and often times it can be found in at an angle that sets it up to be occupying these orbital certain overlaps with these orbitals OK so yeah we talked about this before but the restrictions adhering to hide your bonding and limit the flexibility of the protein backbone it turns out that the flexibility of protein backbone is largely dictated by these hike by hydrogen bonding by the hammered functionalities of the back but let me show you an example of that OK so this
is not just a backbone I've removed all of the amino acid side chains and -dash lines these are the hydrogen bonds notice that many of these hydrogen bonds are coming off the oxygen at an angle that's to take advantage of the Mickey Mouse year shape to the moon pairs on oxygen this fact totally perfect right this is hardly looks Mickey Mouse shit but didn't know can elect making shape this 1 little straighter somebody's look a little more making shape than others case so again you know this is more of a guideline and there's considerable other angles that are available swell and it's is not definite set in stone kind of things that are more like preferences OK so this is the structure of a protein of beta-sheet protein called Conte Haviland I'll talk more about beta-sheets in a moment but it demonstrates the variation the geometry of 100 fonts that's possible all the way from straight to angled but in general angled predominates a notice that on the Huygens Bonser talking about our between NHS of an element from the backbone to the carbon he'll have a background where the dead the Carbondale is a hydrogen bond except the is the hydrogen bond donor exactly what we seen before this kind of to be looks like a zipper writers can like zippers in close and cities high during bonds are relatively weak but when you get enough of them together you get a very very strong interaction like a zipper radio each 1 of those little Hobson the zipper not so strong but uses it the thing up and you get enough strength out of it sets a very similar concept to what we're seeing here each 1 of these maybe half to 1 k cal from old nothing to write home about you put a bunch together now you're talking about big money OK now
another canonical mode for protein backbones is the former helices so we saw on the previous slide that the backbones conform sheets the sheets typically Kirby will talk more about that in a moment In addition the but the hydrogen-bonding preferences can force the backbone of the protein into a Kirby by Felix that looks like that if the Helix has a pitch such that the all residue is interacting with the 4th residue down from away from from its peso if we count I should start at the top OK so over here and if we age of an amino acid is this forming a hydrogen bond with its alone ,comma deal that would give us is weird structure over here OK so the paying the stash lines indicate behind your body we don't see that cases would be by 2 feisty interactions we don't see this at all and protein structures and wife well armed this kind of case the whole thing into a confirmation that's not so comfortable and hydrogen bonds down here can the better satisfy the requirement for overlapping with those loan pairs on oxygen notice over here the lone pairs on oxygen but not so Mickey Bell steered more like coming off on the sides OK so if we interact with the next amino acid the carbon interacting with the 5 plus 1 amino acid that gets us again a kind of twisty looking structure not so strong that is now but the hygiene bonds are terrible angles OK hope something else I should have pointed out that I
didn't notice that the managers are pointing directly at the carbon heels again within those angles that angle really matters a great deal when angle is broken that sets up a much weaker hydrogen-bond I know that's something we've talked about but I want to remind you over here we
kind Eurobonds right angles here set up a very weak hydrogen bonds then ages going off in space 1 way no oxygen carbon fuels is over here does not set up a good hygiene this is to angle similarly over here to wangle where things start to get interesting is when we get to the interactions between Aqaba deal and I residue and an NHL and I plus 3 sets 3 residues away that sets up the page Bonn this nearly the right angle and on this kind of very twisty hillocks is called the 310 he elects its observed we could find 310 hillocks helices there reported in all and cell signaling for binding to for example S H 3 dominates OK so we find us and we'll talk more about those later on and the reason we can find these is that the hydrogen bonds for the 310 Helix not so bad actually write the not so bad because actually the NHS counterpoint in the right direction but there's a kind of a nice the oxygen that the loan here on the oxygen gets to keep standards of Mickey Mouse orbital but this is not so bad as those actually do happen and happen to these 310 helices are very twisty Felix This is a really tightly round out but very tight in Roundhill it's more common Felix is call the hillocks and consists of an interaction between a car beyond all I residue and NIH overnight plus 4 and this gives you hydrogen bonds that had nearly perfect geometry nice Street with each other and so on the south helices are very commonly found it's important motif of proteins secondary structure very very common yet conservative form of yeah OK that's a great question in Ashley OK so Ashley's questionnaires isn't always 1 thing or the other do you sometimes see the 2 things in a converted and the answer is are we largely see it dominates of these Alfie Ulysses and when we look at 310 helices oftentimes will see some flickers of going type was for and then going back type plus 3 in our quest for Atlas Street and so yeah there can be a mixture of the 2 engineers and techniques that you can use like circular digress to follow those 2 and separator out what percentage 310 and what percentage is healthy so interesting OK Our goal here is to maximize the number and the quality of hydrogen bonds between backbone atoms if we do that we're going to have a much more stable secondary structure OK so that's kind of the ultimate goal for everything I'm talking to you about today fun but stopped next
about the offer helices in general How the helices opting clung together with other out helices into large assemblies and it turns out that alpha-helix itself has a dipole associated with that case and you can see this up here and notice that all of the Kerviel's are pointing in the in the same direction each 1 of these has a tiny little dipole associated with that we talked about by polls will talk about dipole interactions much earlier in the quarter but at the time I told you that I polls were and because separations of charge where in this case the oxygen being a little more Elektra negative has a little bit more negative appear and a little bit more positive at the carbon in the carbon deal and said no this little dipole over here in this little guy Felisa Michael all these little by polls are all pointing in the same direction so if you saw up all those little tiny died pulls you end up with a much larger net dipole so the Helix itself has a fairly large that dipole and that means that 1 and has a negative charge in the other and has a positive charge and I would tell you that when I 1st learned about this and it was kind of like Parliament is kind of a mess I've come around entirely and I see the best example of the Kilic Steibel action this is the outer surface of the filamentous bacteria page that's used for phage display it consists of a series about the helices episodes like these 50 amino acid long outfit helices there coiled around each other they're actually Quayle than an unusual arrangement and this is a cross-section through the virus and you can see all the help helices stacking in each other in the very center down here is the DNA of the virus it's not shown I've left it out to make the simpler K but noted that these actually form a right-handed coiled-coil can unfortunately I hate to do this but I'm starting with the major exception to all coiled-coil coils every other coiled-coil there are going to see the spoil this quarter and a fact 99 . 9 9 9 per cent of all oil oils found in nature are left-handed coiled coils this 1 just happens to be a right-handed but here's the thing because each 1 of these helices has has a dipole and all these quails were are pointing in the state the all LP helices pointing in the same direction the virus ends up with a massive negative net negative 0 up Net site net positive charge appear net negative charge down here and the fact is that the virus itself can be oriented in a magnetic field appeared has enough of a dipole that if you put it in an Aymara too because morning an audience in the magnetic field of the Panama to and to me that's pretty persuasive evidence that actually this alpha-helix stuff might have a dipole associated with furthermore when we look at lots of protein structures we find that the positive and of this alpha-helix Paul is oftentimes pointed at the on negative charge of a and functionality in the protein cannot show you an
example of this case so here is a sulfate Adam in a sulfate binding protein and look at these out helices there pointing directly at the sulfate that extra little bit a positive charge could comment and stabilize that negative charge we also find this when we look very closely at enzymes that have to do things like transfer phosphate functionalities which also of negative charge OK let's stop here we come back next time we'll be talking of protein structure and so on my theory topics
Chemische Bindung
Fülle <Speise>
Elektron <Legierung>
Bukett <Wein>
Elektrolytische Dissoziation
Aktives Zentrum
Setzen <Verfahrenstechnik>
Gangart <Erzlagerstätte>
Computational chemistry
Helix <beta->
Energiearmes Lebensmittel
Oxoglutarsäure <2->
Kettenlänge <Makromolekül>
Matrix <Biologie>
Hydrophobe Wechselwirkung
Amine <primär->
Funktionelle Gruppe
Krebs <Medizin>
Dipol <1,3->
Klinisches Experiment
Konkrement <Innere Medizin>
Chemische Struktur
Systemische Therapie <Pharmakologie>
Biologisches Lebensmittel
Aktivität <Konzentration>
Chemische Eigenschaft
Kettenlänge <Makromolekül>
Chemisches Element
Pharmazeutische Chemie
Single electron transfer
Biologisches Lebensmittel
Unterdrückung <Homöopathie>
Optische Aktivität
Modul <Membranverfahren>
Advanced glycosylation end products
Chemische Bindung
Chemische Biologie
Chemischer Prozess
Helix <beta->
Funktionelle Gruppe
Agricultural University of Athens
Helicität <Chemie>
Chemische Formel
Hope <Diamant>
Organische Verbindungen
Radioaktiver Stoff
Posttranslationale Änderung
Chemische Forschung
Coiled coil
Posttranslationale Änderung
Chemische Forschung
Chemische Verbindungen
Pharmazeutische Technologie
Einsames Elektronenpaar
Substrat <Boden>
Primärer Sektor
Chemische Struktur
Chemischer Prozess


Formale Metadaten

Titel Lecture 10. Proteins and Amino Acid Conformations.
Alternativer Titel Proteins and Amino Acid Conformations -- Part 1
Serientitel Chemistry 128: Introduction to Chemical Biology
Teil 10
Anzahl der Teile 18
Autor Weiss, Gregory Alan
Lizenz CC-Namensnennung - Weitergabe unter gleichen Bedingungen 3.0 Unported:
Sie dürfen das Werk bzw. den Inhalt zu jedem legalen und nicht-kommerziellen Zweck nutzen, verändern und in unveränderter oder veränderter Form vervielfältigen, verbreiten und öffentlich zugänglich machen, sofern Sie den Namen des Autors/Rechteinhabers in der von ihm festgelegten Weise nennen und das Werk bzw. diesen Inhalt auch in veränderter Form nur unter den Bedingungen dieser Lizenz weitergeben.
DOI 10.5446/18869
Herausgeber University of California Irvine (UCI)
Erscheinungsjahr 2013
Sprache Englisch

Inhaltliche Metadaten

Fachgebiet Chemie
Abstract UCI Chem 128 Introduction to Chemical Biology (Winter 2013) Instructor: Gregory Weiss, Ph.D. Description: Introduction to the basic principles of chemical biology: structures and reactivity; chemical mechanisms of enzyme catalysis; chemistry of signaling, biosynthesis, and metabolic pathways. Index of Topics: 0:19:40 RNA 0:22:14 Proteins: of Primary Importance 0:28:38 Peptides and Protein are Directional 0:32:39 Useful to Know: pKa Values 0:35:14 Amino Acid Sidechains Dictate Protein Folding and Protein-Protein Interactions 0:42:05 Peptides Can Make Effective Drugs 0:49:29 Chemical Synthesis of Peptides and Proteins 0:59:51 Protein Splicing to Remove Inteins 1:04:31 Protein Structure: The Sum of Lots of Little Forces 1:15:10 a-Helices Form a Dipole

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