9ey4: Difference between revisions
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The | ==The FK1 domain of FKBP51 in complex with (3S,11S)-12-((3,5-dichlorophenyl)sulfonyl)-5-oxo-11-vinyldecahydro-1H-6,10-epiminopyrrolo[1,2-a]azonine-3-carboxamide== | ||
<StructureSection load='9ey4' size='340' side='right'caption='[[9ey4]], [[Resolution|resolution]] 1.16Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9ey4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9EY4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9EY4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.16Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1H78:(1~{S},4~{S},7~{S},8~{S},9~{R})-13-[3,5-bis(chloranyl)phenyl]sulfonyl-8-ethenyl-2-oxidanylidene-3,13-diazatricyclo[7.3.1.0^{3,7}]tridecane-4-carboxamide'>A1H78</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=9ey4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ey4 OCA], [https://pdbe.org/9ey4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ey4 RCSB], [https://www.ebi.ac.uk/pdbsum/9ey4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ey4 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Access to small, rigid, and sp3-rich molecules is a major limitation in the drug discovery for challenging protein targets. FK506-binding proteins hold high potential as drug targets or enablers of molecular glues but are fastidious in the chemotypes accepted as ligands. We here report an enantioselective synthesis of a highly rigidified pipecolate-mimicking tricyclic scaffold that precisely position functional groups for interacting with FKBPs. This was enabled by a 14-step gram-scale synthesis featuring anodic oxidation, stereospecific vinylation, and N-acyl iminium cyclization. Structure-based optimization resulted in the discovery of FKBP inhibitors with picomolar biochemical and subnanomolar cellular activity that represent the most potent FKBP ligands known to date. | |||
Structure-Based Design of Ultrapotent Tricyclic Ligands for FK506-Binding proteins.,Krajczy P, Meyners C, Repity M, Hausch F Chemistry. 2024 Jun 5:e202401405. doi: 10.1002/chem.202401405. PMID:38837733<ref>PMID:38837733</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9ey4" style="background-color:#fffaf0;"></div> | ||
[[Category: Krajczy | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Hausch F]] | |||
[[Category: Krajczy P]] | |||
[[Category: Meyners C]] | |||
Latest revision as of 05:08, 12 June 2024
The FK1 domain of FKBP51 in complex with (3S,11S)-12-((3,5-dichlorophenyl)sulfonyl)-5-oxo-11-vinyldecahydro-1H-6,10-epiminopyrrolo[1,2-a]azonine-3-carboxamide
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