8c74: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8c74]] 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=8C74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C74 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8c74]] 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=8C74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8C74 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=TWX:(3~{R},4~{R})-4-[4-[(4-azanylphenoxy)methyl]-1,2,3-triazol-1-yl]pyrrolidin-3-ol'>TWX</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.15Å</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=TWX:(3~{R},4~{R})-4-[4-[(4-azanylphenoxy)methyl]-1,2,3-triazol-1-yl]pyrrolidin-3-ol'>TWX</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=8c74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c74 OCA], [https://pdbe.org/8c74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c74 RCSB], [https://www.ebi.ac.uk/pdbsum/8c74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c74 ProSAT]</span></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=8c74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8c74 OCA], [https://pdbe.org/8c74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8c74 RCSB], [https://www.ebi.ac.uk/pdbsum/8c74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8c74 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 12:31, 17 October 2024
Pyrrolidine fragment 10d bound to endothiapepsinPyrrolidine fragment 10d 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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