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Organometallic enzyme inhibitors

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Automatisierte Medienanalyse

Erkannte Entitäten
but the meaning the ruling in the the a the in the in the a few years
ago we thought about that the
concept new concept to basically designed Willard defined structures by using metal scaffolds to make small molecules it's as close to a small molecule inhibitors for 4
enzymes and you can see here in representation here and metal compounds in which the Met has just a structural it basically helps too basically organized organic ligands and in active side and it's basically really like structures center and exciting part for us about this is that of course methods can have coordination geometries that differ from the coordination geometries of carbon where you behind limited to linear trade the planet etcetera he drew up a coordination here and there and I think we have shown over the last couple of years that this is really a promising approach and be designed actually call points that have pulled sees that can I really compete in their classes with the best organic components available in sometimes in some cases we think we have compensated better than the best organic compounds for respective talks and I want to show you yeah maybe was 1 designed that we develop a few years ago in which we are developed reporting kindness inhibit us by using a natural product as an inspiration you can see here on the left side and after
work South Korea which is an indoor cover the likely we used use these to indoor it and then you have a couple hundred more IT in this call .period actually finds true approaching kindness ATP binding said in an ATP competitive fashion this heater slightly moieties slides into the active site in Cannes the form to Hysham belongs to a quarter inch regional offices but um at Peabody said and then the active site opens and this morgue will are carbohydrates can feel this is the area where resin rivals was moiety of ATP binds and we basically used assistant operations and and designed compounds that have similar shape but are simple and their design and container medical upon its you can see here and you see that this will be "quotation mark real covers or is quite similar to this in Oracle was only just basically replaced 1 in willful purity that gives us 2 to coordination sides and we can introduce users Racine fragment you can see that this type of printer .period dining have sent which and CEO and this component actually turns out to be a very important inhibitor for this kind of Steve case to be achieved by a factor of 10 for better than the natural products and over the years he actually improved the design and we ended up actually was a "quotation mark .period as shown here that has a CKI there is less than 5 Pecanwood so this
again metallic component is actually buy around the fall of 3 to 4 as of magnitude more potent than this support that report and it's very selected for this particular protein kind as you can even see here um uh that proved to cope with the structure of this
organ in the telecom born with this kind of Steve case 3 and holders ,comma .period really complements nicely the shape of his ATP binding site off this kind Steve case Street and you can actually I think you probably agree with me that this is the unique morning class structure that you probably cannot mainly with purely organic elements you have to this this was he and that really pretty sits on the site of the Dynamo mighty in the middle and basically a bit more to the born to individual comes of succeed here so that was actually far as a very exciting time should I a direction in in this award porch again encouraged us it really using methods as structures scaffolds is very promising and I can tell you what he called 1 hour chemically various state you can use a items and not compromise in any way in a biological samples stable in presence of Cyrus sustained against water oxygen so such call basically I stateless organic
compounds suggests they defend the color instead of being white and yellow they are many purple black was sentenced blue or green so and that's the only basically a difference if you that is often but that looks like a nice system but we we knew was that these half-percentage components but some are still limit in the structure options and we were really actually uh we sought it's important to move ahead and to basically expenses stalwarts truly to hear points because if you opened here and that you can't from 6 spots and that's kind of beautiful because communal ,comma that can from 6 six-point deal ,comma that can follow object here coordination geometries you cannot you cannot form stated organic compounds where :colon can make 6 spots but a lot of Medicare and if you that talk about proscenium uniforms very stable after he the coordination geometries and we want to use Racine and compounds also in it but in some respects a real human Austin cope and Warren command s basically makes for Ricardo and what we the reason that think that such a to hear conditions here is sold as promising and interesting for making small molecule inhibitors because think about it and opted uterus center that has 6 more at Lincoln's connection from up to certify their is missing you he is he's listed all searches their eyes a :colon Kneser ,comma can just formed to Astaire estimates the from 4 substitutions 26 as the number of their isomers increases by more than an order of magnitude form to 250 and the number of stare isomers search in this case basically is an indicator of how sophisticated such a center is true basically people structure because we have certainly ways to organize the 6 groups In the three-dimensional space so very sophisticated structure center if you take 2 of the centers you can make 900 rising rest if you 6 and 3 center you can from and 327 thousand tourists so the number of sterilize is in a certain way in indicator of complicated and then you look at complicated natural that as she can't patrons from this if you have a complicated
reportedly look at the number of terrorism and that gives you a certain idea of how complicated the structures and harmonize their asthma as you could fall and so forth that that is basically our hypothesis for making such open your compile and that this was the focus of the last 2 years in particular since the and mob over the last 2 weeks 2 years we really focus on moving away From this half-percentage components to to hear compost half-cent which was nice because they have the U.S. cemetery they don't have so many there reason was a good starting point but now we really want to go and complicated optical components and and want to explore the potential to become the mayor bioactive points that can do sophisticated Monica recognition and and I want to just give you 1 example of a recent designed that I think shows very nicely a whole big powerful such an approach that we we have a carburetor Warner mom was done at the Wistar Institute in Philadelphia he he is very interested in this party can expect 1 and so what we did is we found that we be attacked took a small library that we have a lot and that the standard library of again a metallic components with against kindness and found that this comp once yet and piecemeal 9 is wasn't this library is the most potent company for this kind this scaffold looks an area that is stated in Fiji's case meaning that I showed you on this on this image and so this complicated 9 turned out to be actually quite decent inhibitor for picked 1009 1 Mike amortizing 50 that's considered a very nice primary at however is that would you before this scare very poor for GSK Street this
company in particular weight once indoor furring of the Prudy basically has IC 50 of steel that 50 people were effigies so you would imagine that you can never much modify the scaffold and make it selected for the kind of pick 1 over Jesus history seems to be mission impossible however anyways we we went ahead and just now and from from my group and 1 group she call crystallizes Kompong respect 1 and you can see here the crystal structure in particular what was exciting for us we saw all the heightened warns that this call .period bathing undergoes as we expected but
however when you look at the cuts through the active site you
see that perspective said is very old and the CPU ring here shown as suspects fitting model does not undergo any into actions at the site just barely hangs there in a free space and can just not this large active site so we thought that the she great modern system to to investigate the power of the Lotte Shopping fewer components and we just use this Lead structure and replaces CP for this a large violated legal and current you can see the space that this election he blew up the structure and indeed be found by doing so actually this component initially very selective Agee's K Street after this change this call but actually it's a 10 for it's better for Pak Wan and suddenly it's basically not inhibit effigies of me anymore because it just looked fit and is in site and the great of light by caucuses structure again the done by just now and you can see all the height bonds in what is
most important you can see here again and discussed with decide that now this logical .period can really nicely complements this old open and filter completely and the distance between the proposition of security and see all these Iraq's 8 Angstrom the like like got stake that basically determines whether the company can fit Internet decided not to use case is not old of it very not fit into their but picked 1 of old method can no longer go all these interactions that I'm portent for the affinity and selectively so and and and I think that is a on knowledge this come here which recall effort for you is actually the
best ATP competitive inhibitor for the supporting kindness today better than any reported purely organic compost and it's not an organic components it's just accordionist of the Allah you the a little take me to do and you get a Of the you could In a letter to the
Biologisches Material
Chemische Bindung
Metallorganische Verbindungen
Chemische Forschung
Chemische Verbindungen
Chemische Struktur
Funktionelle Gruppe
Containment <Gentechnologie>
Systemische Therapie <Pharmakologie>
Aktives Zentrum
Biologisches Lebensmittel
Aktivität <Konzentration>
Potenz <Homöopathie>
Setzen <Verfahrenstechnik>
Scaffold <Biologie>
Oxoglutarsäure <2->
Chemisches Element


Formale Metadaten

Titel Organometallic enzyme inhibitors
Serientitel Chymiatrie
Autor Meggers, Eric
Jerabek, Paul
Hegemann, Julian
Authmann, Andreas
Lizenz CC-Namensnennung - keine kommerzielle Nutzung - Weitergabe unter gleichen Bedingungen 3.0 Deutschland:
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DOI 10.5446/18747
Herausgeber Paul Jerabek, Julian Hegemann, Andreas Authmann
Erscheinungsjahr 2009
Sprache Englisch

Inhaltliche Metadaten

Fachgebiet Chemie
Abstract Professor Meggers explains a novel approach to the synthesize of enzyme inhibitors, where his group is utilizing the unique properties of ruthenium based organometallic compounds.
Schlagwörter Organik

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