Evaluation of triazolamers as active site inhibitors of HIV-1 protease

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 21; pp. 6023 - 6026
• Main Authors: Jochim, Andrea L., Miller, Stephen E., Angelo, Nicholas G., Arora, Paramjit S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.11.2009; Elsevier
• Subjects: Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Catalytic Domain; Computer Simulation; HIV Protease - chemistry; HIV Protease - metabolism; HIV Protease Inhibitors - chemistry; HIV Protease Inhibitors - pharmacology; Human immunodeficiency virus 1; Humans; Medical sciences; Peptidomimetics; Pharmacology. Drug treatments; Protease inhibitor; Software; Triazoles - chemistry; Triazoles - pharmacology; β-Strand mimetics; β-Strand mimetics; Peptidomimetics; Protease inhibitor; HIV-1 virus; Enzyme; Peptidomimetic compound; Active site; Retroviridae; Enzyme inhibitor; Inhibitor enzyme complex; Oligomer; Lentivirus; In vitro; Modeling; Virus; Peptidases; Triazole derivative polymer; Structure activity relation; Molecular model; Hydrolases; Antiviral; Human immunodeficiency virus
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.09.049

Design of nonpeptidic β-strand mimetics as protease inhibitors is reported. Proteases typically recognize their peptide substrates in extended conformations. General approaches for designing protease inhibitors often consist of peptidomimetics that feature this conformation. Herein we discuss a combination of computational and experimental studies to evaluate the potential of triazole-linked β-strand mimetics as inhibitors of HIV-1 protease activity.