8c6p: Difference between revisions
New page: '''Unreleased structure''' The entry 8c6p is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Fragment screening hit I bound to endothiapepsin== | |||
<StructureSection load='8c6p' size='340' side='right'caption='[[8c6p]], [[Resolution|resolution]] 1.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8c6p]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8C6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C6P FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=TT6:4-[(2-azanyl-4-methyl-1,3-thiazol-5-yl)methyl]benzenecarbonitrile'>TT6</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8c6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c6p OCA], [https://pdbe.org/8c6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c6p RCSB], [https://www.ebi.ac.uk/pdbsum/8c6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c6p ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Fragment-based drug discovery has played an important role in medicinal chemistry and pharmaceutical research. Despite numerous demonstrated successes, the limited diversity and overrepresentation of planar, sp(2)-rich structures in commercial libraries often hamper the full potential of this approach. Hence, the thorough design of screening libraries inevitably determines the probability for meaningful hits and subsequent structural elaboration. Against this background, we present the generation of an exclusive fragment library based on iterative entry nomination by a specifically designed computational workflow: "Fragtory". Following a pharmacophore diversity-driven approach, we used Fragtory in an interdisciplinary academic setting to guide both tailored synthesis efforts and the implementation of in-house compounds to build a curated 288-member library of sp(3)-enriched fragments. Subsequent NMR screens against a model protein and hit validation by protein crystallography led to the identification of structurally novel ligands that were further characterized by isothermal titration calorimetry, demonstrating the applicability of our experimental approach. | |||
Fragtory: Pharmacophore-Focused Design, Synthesis, and Evaluation of an sp(3)-Enriched Fragment Library.,Buhrmann M, Kallepu S, Warmuth JD, Wiese JN, Ehrt C, Vatheuer H, Hiller W, Seitz C, Levy L, Czodrowski P, Sievers S, Muller MP, Rauh D J Med Chem. 2023 May 11;66(9):6297-6314. doi: 10.1021/acs.jmedchem.3c00187. Epub , 2023 May 2. PMID:37130057<ref>PMID:37130057</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8c6p" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cryphonectria parasitica]] | |||
[[Category: Large Structures]] | |||
[[Category: Buehrmann M]] | |||
[[Category: Mueller MP]] | |||
[[Category: Rauh D]] | |||
[[Category: Wiese JN]] | |||
Latest revision as of 07:02, 25 May 2023
Fragment screening hit I bound to endothiapepsinFragment screening hit I bound to endothiapepsin
Structural highlights
FunctionPublication Abstract from PubMedFragment-based drug discovery has played an important role in medicinal chemistry and pharmaceutical research. Despite numerous demonstrated successes, the limited diversity and overrepresentation of planar, sp(2)-rich structures in commercial libraries often hamper the full potential of this approach. Hence, the thorough design of screening libraries inevitably determines the probability for meaningful hits and subsequent structural elaboration. Against this background, we present the generation of an exclusive fragment library based on iterative entry nomination by a specifically designed computational workflow: "Fragtory". Following a pharmacophore diversity-driven approach, we used Fragtory in an interdisciplinary academic setting to guide both tailored synthesis efforts and the implementation of in-house compounds to build a curated 288-member library of sp(3)-enriched fragments. Subsequent NMR screens against a model protein and hit validation by protein crystallography led to the identification of structurally novel ligands that were further characterized by isothermal titration calorimetry, demonstrating the applicability of our experimental approach. Fragtory: Pharmacophore-Focused Design, Synthesis, and Evaluation of an sp(3)-Enriched Fragment Library.,Buhrmann M, Kallepu S, Warmuth JD, Wiese JN, Ehrt C, Vatheuer H, Hiller W, Seitz C, Levy L, Czodrowski P, Sievers S, Muller MP, Rauh D J Med Chem. 2023 May 11;66(9):6297-6314. doi: 10.1021/acs.jmedchem.3c00187. Epub , 2023 May 2. PMID:37130057[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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