7to5
From Proteopedia
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==HIV-1 wild type protease with GRL-05816A, with C-4 substituted cyclohexane-fused bis-tetrahydrofuran (Chf-THF) derivatives as P2-ligand [diastereomer 1]== | ==HIV-1 wild type protease with GRL-05816A, with C-4 substituted cyclohexane-fused bis-tetrahydrofuran (Chf-THF) derivatives as P2-ligand [diastereomer 1]== | ||
| - | <StructureSection load='7to5' size='340' side='right'caption='[[7to5]]' scene=''> | + | <StructureSection load='7to5' size='340' side='right'caption='[[7to5]], [[Resolution|resolution]] 1.13Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TO5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7to5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TO5 FirstGlance]. <br> |
| - | </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=7to5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7to5 OCA], [https://pdbe.org/7to5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7to5 RCSB], [https://www.ebi.ac.uk/pdbsum/7to5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7to5 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=G8R:(1R,3aS,4S,6S,7aR)-octahydro-1,6-epoxy-2-benzofuran-4-yl+[(2S,3R)-4-{[2-(cyclopropylamino)-1,3-benzothiazole-6-sulfonyl](2-methylpropyl)amino}-3-hydroxy-1-phenylbutan-2-yl]carbamate'>G8R</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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"><div style='overflow: auto; max-height: 3em;'>[[2ien|2ien]], [[6bz2|6bz2]], [[6vod|6vod]], [[6voe|6voe]], [[7to6|7to6]]</div></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=7to5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7to5 OCA], [https://pdbe.org/7to5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7to5 RCSB], [https://www.ebi.ac.uk/pdbsum/7to5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7to5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The design, synthesis, X-ray structural, and biological evaluation of a series of highly potent HIV-1 protease inhibitors are reported herein. These inhibitors incorporated novel cyclohexane-fused tricyclic bis -tetrahydrofuran as P2 ligands in combination with a variety of P1 and P2'-ligands. Compound 4d with a difluoromethylphenyl P1 ligand and a cyclopropylaminobenzothiazole P2' ligand exhibited the most potent antiviral activity. Also, it maintained highly potent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The corresponding inhibitor 5d with an enantiomeric ligand was significantly less potent in these antiviral assays. The new P2 ligands were synthesized in optically active form using enzymatic desymmetrization of meso -diols as the key step. To obtain molecular insight, high resolution X-ray structures of inhibitors 4b and 5d -bound HIV-1 protease were determined and structural analyses are highlighted here. | ||
| + | |||
| + | Design, Synthesis and X-ray Structural Studies of Potent HIV-1 Protease Inhibitors Containing C-4 Substituted Tricyclic Hexahydro-furofuran derivatives as P2 ligands.,Ghosh AK, Kovela S, Sharma A, Shahabi D, Ghosh AK, Hopkins DR, Yadav M, Johnson ME, Agniswamy J, Wang YF, Aoki M, Amano M, Weber IT, Mitsuya H ChemMedChem. 2022 Feb 15. doi: 10.1002/cmdc.202200058. PMID:35170223<ref>PMID:35170223</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7to5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Agniswamy J]] | + | [[Category: Agniswamy, J]] |
| - | [[Category: Ghosh | + | [[Category: Ghosh, A K]] |
| - | [[Category: Wang Y | + | [[Category: Wang, Y F]] |
| - | [[Category: Weber | + | [[Category: Weber, I T]] |
| + | [[Category: Antiviral protein]] | ||
| + | [[Category: Antiviral protein-inhibitor complex]] | ||
| + | [[Category: Aspartic acid protease]] | ||
| + | [[Category: Hiv-1 protease]] | ||
| + | [[Category: Inhibitor]] | ||
Revision as of 07:25, 16 March 2022
HIV-1 wild type protease with GRL-05816A, with C-4 substituted cyclohexane-fused bis-tetrahydrofuran (Chf-THF) derivatives as P2-ligand [diastereomer 1]
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