7yf6: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7yf6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YF6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7yf6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YF6 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHL:2-AMINO-ETHANETHIOL'>DHL</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.01Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHL:2-AMINO-ETHANETHIOL'>DHL</scene>, <scene name='pdbligand=MEA:N-METHYLPHENYLALANINE'>MEA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7yf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yf6 OCA], [https://pdbe.org/7yf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yf6 RCSB], [https://www.ebi.ac.uk/pdbsum/7yf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yf6 ProSAT]</span></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=7yf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yf6 OCA], [https://pdbe.org/7yf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yf6 RCSB], [https://www.ebi.ac.uk/pdbsum/7yf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yf6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 14:20, 15 November 2023
Crystal structure of HIV-1 protease in complex with macrocyclic peptideCrystal structure of HIV-1 protease in complex with macrocyclic peptide
Structural highlights
FunctionPublication Abstract from PubMedHuman immunodeficiency virus type-1 (HIV-1) protease is essential for viral propagation, and its inhibitors are key anti-HIV-1 drug candidates. In this study, we discovered a novel HIV-1 protease inhibitor (compound 16) with potent antiviral activity and oral bioavailability using a structure-based drug design approach via X-ray crystal structure analysis and improved metabolic stability, starting from hit macrocyclic peptides identified by mRNA display against HIV-1 protease. We found that the improvement of the proteolytic stability of macrocyclic peptides by introducing a methyl group to the alpha-position of amino acid is crucial to exhibit strong antiviral activity. In addition, macrocyclic peptides, which have moderate metabolic stability and solubility in solutions containing taurocholic acid, exhibited desirable plasma total clearance and oral bioavailability. These approaches may contribute to the successful discovery and development of orally bioavailable peptide drugs. Highly Potent and Oral Macrocyclic Peptides as a HIV-1 Protease Inhibitor: mRNA Display-Derived Hit-to-Lead Optimization.,Kusumoto Y, Hayashi K, Sato S, Yamada T, Kozono I, Nakata Z, Asada N, Mitsuki S, Watanabe A, Wakasa-Morimoto C, Uemura K, Arita S, Miki S, Mizutare T, Mikamiyama H ACS Med Chem Lett. 2022 Sep 1;13(10):1634-1641. doi:, 10.1021/acsmedchemlett.2c00310. eCollection 2022 Oct 13. PMID:36262395[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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