5u6e: Difference between revisions
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==Crystal structure of clade A/E HIV-1 gp120 core in complex with NBD-14010== | |||
<StructureSection load='5u6e' size='340' side='right' caption='[[5u6e]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5u6e]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U6E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U6E FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=82M:N-{(1S)-2-AMINO-1-[5-(HYDROXYMETHYL)-4-METHYL-1,3-THIAZOL-2-YL]ETHYL}-5-(4-CHLORO-3-FLUOROPHENYL)-1H-PYRROLE-2-CARBOXAMIDE'>82M</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=5u6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6e OCA], [http://pdbe.org/5u6e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u6e RCSB], [http://www.ebi.ac.uk/pdbsum/5u6e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6e ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In our attempt to optimize the lead HIV-1 entry antagonist, NBD-11021, we present in this study the rational design and synthesis of 60 new analogues and determination of their antiviral activity in a single-cycle and a multicycle infection assay to derive a comprehensive structure-activity relationship (SAR). Two of these compounds, NBD-14088 and NBD-14107, showed significant improvement in antiviral activity compared to the lead entry antagonist in a single-cycle assay against a large panel of Env-pseudotyped viruses. The X-ray structure of a similar compound, NBD-14010, confirmed the binding mode of the newly designed compounds. The in vitro ADMET profiles of these compounds are comparable to that of the most potent attachment inhibitor BMS-626529, a prodrug of which is currently undergoing phase III clinical trials. The systematic study presented here is expected to pave the way for improving the potency, toxicity, and ADMET profile of this series of compounds with the potential to be moved to the early preclinical development. | |||
Synthesis, Antiviral Potency, in Vitro ADMET, and X-ray Structure of Potent CD4 Mimics as Entry Inhibitors That Target the Phe43 Cavity of HIV-1 gp120.,Curreli F, Kwon YD, Belov DS, Ramesh RR, Kurkin AV, Altieri A, Kwong PD, Debnath AK J Med Chem. 2017 Mar 16. doi: 10.1021/acs.jmedchem.7b00179. PMID:28266845<ref>PMID:28266845</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: Debnath, A | <div class="pdbe-citations 5u6e" style="background-color:#fffaf0;"></div> | ||
[[Category: Kwon, Y | == References == | ||
[[Category: Kwong, P | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Debnath, A K]] | |||
[[Category: Kwon, Y D]] | |||
[[Category: Kwong, P D]] | |||
[[Category: Hiv-1]] | |||
[[Category: Nbd-14010]] | |||
[[Category: Small molecule]] | |||
[[Category: Viral protein]] | |||
[[Category: Virus entry antagonist]] | |||
Revision as of 07:39, 27 April 2017
Crystal structure of clade A/E HIV-1 gp120 core in complex with NBD-14010
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