6e9a: Difference between revisions
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==HIV-1 WILD TYPE PROTEASE WITH GRL-034-17A, (3aS, 5R, 6aR)-2-OXOHEXAHYD CYCLOPENTA[D]-5-OXAZOLYL URETHANE WITH A BICYCLIC OXAZOLIDINONE SCAFF AS THE P2 LIGAND== | |||
<StructureSection load='6e9a' size='340' side='right' caption='[[6e9a]], [[Resolution|resolution]] 1.22Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6e9a]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E9A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E9A FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=J0S:(3aS,5R,6aR)-2-oxohexahydro-2H-cyclopenta[d][1,3]oxazol-5-yl+[(2S,3R)-3-hydroxy-4-{[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino}-1-phenylbutan-2-yl]carbamate'>J0S</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ien|2ien]], [[6e7j|6e7j]]</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e9a OCA], [http://pdbe.org/6e9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e9a RCSB], [http://www.ebi.ac.uk/pdbsum/6e9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e9a ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We have designed, synthesized, and evaluated a new class of potent HIV-1 protease inhibitors with novel bicyclic oxazolidinone derivatives as the P2 ligand. We have developed an enantioselective synthesis of these bicyclic oxazolidinones utilizing a key o-iodoxybenzoic acid mediated cyclization. Several inhibitors displayed good to excellent activity toward HIV-1 protease and significant antiviral activity in MT-4 cells. Compound 4k has shown an enzyme Ki of 40 pM and antiviral IC50 of 31 nM. Inhibitors 4k and 4l were evaluated against a panel of highly resistant multidrug-resistant HIV-1 variants, and their fold-changes in antiviral activity were similar to those observed with darunavir. Additionally, two X-ray crystal structures of the related inhibitors 4a and 4e bound to HIV-1 protease were determined at 1.22 and 1.30 A resolution, respectively, and revealed important interactions in the active site that have not yet been explored. | |||
Design and Synthesis of Potent HIV-1 Protease Inhibitors Containing Bicyclic Oxazolidinone Scaffold as the P2 Ligands: Structure-Activity Studies and Biological and X-ray Structural Studies.,Ghosh AK, Williams JN, Ho RY, Simpson HM, Hattori SI, Hayashi H, Agniswamy J, Wang YF, Weber IT, Mitsuya H J Med Chem. 2018 Oct 24. doi: 10.1021/acs.jmedchem.8b01227. PMID:30354121<ref>PMID:30354121</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6e9a" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Agniswamy, J]] | [[Category: Agniswamy, J]] | ||
[[Category: Weber, I | [[Category: Wang, Y F]] | ||
[[Category: Weber, I T]] | |||
[[Category: Antiviral]] | |||
[[Category: Hiv-1 protease inhibitor of grl-034-17a]] | |||
[[Category: Hydrolase]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Multidrug-resistant]] | |||
[[Category: Oxazolidinone]] | |||
[[Category: P2 ligand]] | |||
[[Category: Viral protein]] | |||
