7yf6

Crystal structure of HIV-1 protease in complex with macrocyclic peptide

spinqualitylabelsall models 7yf6, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yf6 is a 3 chain structure with sequence from Human immunodeficiency virus 1 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.01Å Ligands: DHL, MEA, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9WFL7_9HIV1 Publication Abstract from PubMed Human 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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