View source for 5wlo


==a novel 13-ring macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands==
<StructureSection load='5wlo' size='340' side='right'caption='[[5wlo]], [[Resolution|resolution]] 1.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wlo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WLO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WLO 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]] 1.27&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=GR7:(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl+{(2S,3R)-3-hydroxy-4-[(7E)-13-methoxy-1,1-dioxo-1,4,5,6,9,11-hexahydro-10,1lambda~6~,2-benzoxathiazacyclotridecin-2(3H)-yl]-1-phenylbutan-2-yl}carbamate'>GR7</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5wlo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wlo OCA], [https://pdbe.org/5wlo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wlo RCSB], [https://www.ebi.ac.uk/pdbsum/5wlo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wlo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q72498_9HIV1 Q72498_9HIV1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (Ki=13.2nM, IC50=22nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. These compounds showed excellent HIV-1 protease inhibitory (Ki=62pM and 14pM, respectively) and antiviral activity (IC50=5.3nM and 2.0nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.

Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands.,Ghosh AK, Sean Fyvie W, Brindisi M, Steffey M, Agniswamy J, Wang YF, Aoki M, Amano M, Weber IT, Mitsuya H Bioorg Med Chem Lett. 2017 Sep 6. pii: S0960-894X(17)30892-2. doi:, 10.1016/j.bmcl.2017.09.003. PMID:28958624<ref>PMID:28958624</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5wlo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Agniswamy J]]
[[Category: Wang Y-F]]
[[Category: Weber IT]]