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Nobel Prize in Chemistry Awarded to Bertozzi, Meldal, and Sharpless
- downvotetruth 4y agoTalk about an undeserving "click" as if other reactions do not. Let's award a patent portfolio. Scripps must be tickled pink.
- DrAwdeOccarim 4y agoFor those who are just first learning about click chemistry, it makes attaching two larger molecules together very, very simple. It can be done under very gentle conditions (like in water), and has exceptional selectivity. Like it's so selective you really don't need to worry about other things happening on the timescales these reactions occur and can be cleaned up (an hour). There are two types of click chemistry, one that uses copper as a catalyst and one that doesn't. They both opened the world of chemically "stapling" two things together to literally all bench scientists. I cannot overstate how transformative this has been to biological science.
- tgv 4y agoYou mean: LEGO-like chemistry? Wow, I'd never heard of that. Any info on how and what-for it's used in practice?
- j7ake 4y agoFor example, attaching fluorophores to molecules so you can track them in a microscope.
- lepetitpedre 4y agoOf course a Danish person got LEGO into chemistry
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- dmix 4y agoDo you have an example of some molecules that would be joined in an experiment?
- hirenj 4y agoA specific example would describe Bertozzi's work - where sugars with a chemical "handle" are installed on to the cell surface. You can then click something like a fluorophore onto the sugars with handles to figure out where these specific sugars are on a cell surface.
- zasdffaa 4y agoAh, so we're definitely not talking bolting together the little stuff, like pyrrole + benzene ring kind of thing?
- throwawaymaths 4y agoYou can do that (glue together two tiny molecules of arbitrary size) but the connector that you get that joins the two pieces in the resulting molecule is not arbitrary.
- throwawaymaths 4y agoI'm not aware of any major discoveries that have come about from this technique. Can someone correct me? I'd accept: - elucidating a new signal transduction pathway - discovering an uncharacterized enzyme - measuring a biochemical constant of a known molecule (Kd e.g.) - discovering a new drug target that then gets exploited
- jfarlow 4y agoUsing the above chemistry, you can attach DNA oligos to lipids, DNA oligos to proteins, fluorophores to DNA, fluorophores to proteins at particular locations or other complex drugs to DNA, protein or lipids. Once you get DNA oligos in there you can do computation, as X binds X', and Y to Y'. So you can have all sorts of complex synthetic & designed interactions using chemistry that is both seamless and doesn't interfere with normal molecular biolgy. Once you have proteins, you can localize particular chemistries.
- ak_111 4y agoThis sounds mind-blowing and if it is transformative as you state, then why did it take so long to award it the prize, have all the most recent previous winners been more worthy?
- wholinator2 4y agoIt can sometimes take a long time to get a prize awarded. Like I believe Einstein didn't get his prize for years and years after he discovered Relativity and even when they awarded it to him it was only for the photo electric effect, which while important, wasn't perceived as his largest contribution
- btilly 4y agoHe didn't get it for relativity in part because of a well-known philosopher. See https://nautil.us/this-philosopher-helped-ensure-there-was-no-nobel-for-relativity-235898/ https://nautil.us/this-philosopher-helped-ensure-there-was-n... for the story.
- dekhn 4y ago"only" for the photoelectric effect? That was one of the most fundamental scientific discoveries (well, explanation for an unexpected failure of theory to predict experiment) of all time. In particular, the idea of wave packets replacing particle and wave representations was quite helpful.
- ceejayoz 4y agoThat's entirely normal. https://www.nature.com/articles/508186a https://www.nature.com/articles/508186a > Before 1940, Nobels were awarded more than 20 years after the original discovery for only about 11% of physics, 15% of chemistry and 24% of physiology or medicine prizes, respectively. Since 1985, however, such lengthy delays have featured in 60%, 52% and 45% of these awards, respectively.
- throwawaymaths 4y agoIt's very cool but not that transformative. I don't know of any major biological discovery that depended on it. Honestly imo the coolest click chemistry application was as a two-component bonding glue for copper pieces
- coolspot 4y agoCan it simplify DIY drug/explosive production?
- chrisbrandow 4y agoI guess it depends on your definition of DIY. It's not new, so if someone didn't already know about it, then they are probably unlikely to be in a position to take advantage of it, because it is already how a lot of synthesis in this field is done.
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- elsjaako 4y agoThis sounds like a very interesting technique. Does anyone know of a Scientific American level explanation that goes into a bit of depth about this?
- lmz 4y agohttps://www.nobelprize.org/uploads/2022/10/popular-chemistryprize2022.pdf https://www.nobelprize.org/uploads/2022/10/popular-chemistry... is linked from the page
- subroutine 4y agoWikipedia article: https://en.wikipedia.org/wiki/Click_chemistry https://en.wikipedia.org/wiki/Click_chemistry
- elsjaako 4y agoThanks, exactly the kind of thing I'm going for. The site is pretty confusing thought, I don't think I could have found it myself. Now I know the link exists I can find it, but I think putting it behind a dropdown on a box labeled "Summary", and labeling it "Popular Chemistry" isn't great for having people find it.
- ranguna 4y ago> Scientific American level explanation Imagine lego, but with chemistry.
- twobitshifter 4y agoThis is the second nobel prize for Sharpless. He won in 2001 as well.
- ttrrooppeerr 4y agoNo relevant user...surname?
- vixen99 4y agoAs with Fred Sanger (chemistry) and John Bardeen (physics) who also won twice in the same category.
- sizzzzlerz 4y agoI wonder if, as a child, he was ever told that he wouldn't amount to much.
- keithalewis 4y agoRosebud
- melagonster 4y agomaybe this is why his second so late... when Sanger fourth perform important found on sequencing something, council told him some like: "we know it is important, but bro you had have three on secequcing something".
- hoseja 4y ago
- MagnumOpus 4y agoNot that much off the mark: https://www.ki.ku.dk/Nyheder/Nyhedssamling/crystal_ball_15/NCBWinner300x200.jpg https://www.ki.ku.dk/Nyheder/Nyhedssamling/crystal_ball_15/N...
- dmix 4y agoThat's a much nicer photo IMO. It just seems very accentuated when it's drawn with hard lines.
- netrus 4y agoThe portraits are usually based on the first nice looking picture in the Google Image search. In Morten's case they appear to have mirrored it :)
- dom96 4y agoI disagree. I think it's a cool illustration and he looks good in it.
- boomboomsubban 4y agoThat was my first thought, and then I was amazed at how dominant the Nobel photo was in a DDG image search 30 minutes after it was announced. Now a few hours later and it's only Nobel affiliated pictures in the first ~50.
- nh23423fefe 4y agoI'm sure he is crying about it on instagram
- tchalla 4y agoThis is the second Nobel Prize in Chemistry awarded to Karl Barry Sharpless. In 2001, he was awarded half of the Chemistry prize “for his work on chirally catalysed oxidation reactions”. https://www.nobelprize.org/prizes/chemistry/2001/press-release/ https://www.nobelprize.org/prizes/chemistry/2001/press-relea... https://en.wikipedia.org/wiki/Karl_Barry_Sharpless https://en.wikipedia.org/wiki/Karl_Barry_Sharpless
- chrisbrandow 4y agohe's up to 5/6 of a solo Nobel prize now, since he was technically awarded half of his first prize. I haven't looked yet at how many people have been awarded multiple Nobels in the same field.
- chrisbrandow 4y agoI guess I should have read the comments below first. :-)
- COGlory 4y agoPeople are missing the point. It's not the click that matters. It's the bio-orthogonal part. This lets me grow cells with one of the click substrates, say, a methionine substitute that incorporates into every protein, purify out my protein, and then easily do chemistry on that. That's near invaluable. I can grow a virus and put a different click substrate in each of the DNA, protein, and lipids. Then I can infect cells, and mid-infection, separately label each macromolecule a different color. Then, I can figure out what parts of the virus go into the cell, which sheds light on the mechanism of entry. Having it bio-orthogonal means the biology is preserved and nothing is messed up until the moment of observation.
- panabee 4y agoThanks for the explanation. This seems amazing, but could you kindly clarify how adding glycans to a cell is guaranteed to not disturb biological function?
- throwawaymaths 4y agoWhat "different click substrates" are you talking about? As far as I remember There's only one class that's been developed (alkyne azide cycloaddition) -- sharpless really wants norbornene to take off but no one has developed that afaict - and of these only one that can be done in vivo (cyclooctyne + azide); the others require copper catalyst which is not awesome for living cells. > ... methionine substitute that incorporates into every protein, purify out This is crazy labor intensive, I feel like if you are at this point in considering using this to understand a biological you have really burned through a lot of simpler, more established, and easy to calibrate techniques.
- sdbrown 4y agoTetrazine/DBCO is also pretty popular IIRC.
- throwawaymaths 4y agoFair. This holds a place in my mind as "basically the same as alkyne - azide" since Tetrazzine is "more or less azide" and dbco is "more or less cyclooctyne". More to the point of the thread, I don't think the Tetrazzine/dbco is orthogonal to alkyne-azide -- they will cross-react -- am I wrong about that?
- wrd 4y agoFormer chemist here. I worked in a lab where our main goal was to attach a special fluorophore (= fluorescent molecular probe) to a protein so we could observe how it changes conformation under different conditions. The way we did that was with click chemistry: we incorporated a synthetic amino acid (homopropargylglycine) into the protein and then used a copper-catalyzed click reaction to attach the probe to the synthetic amino acid. (Specifically this reaction: https://en.wikipedia.org/wiki/Click_chemistry#Copper(I)-catalyzed_azide-alkyne_cycloaddition_(CuAAC) https://en.wikipedia.org/wiki/Click_chemistry#Copper(I)-cata...). It's definitely cool stuff.
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- alpineidyll3 4y agoThe exception: a well deserved nobel prize.