Design of a Novel HIV-1 Fusion Inhibitor That Displays a Minimal Interface for Binding Affinity

• Published in: Journal of medicinal chemistry Vol. 51; no. 3; pp. 388 - 391
• Main Authors: Oishi, Shinya, Ito, Saori, Nishikawa, Hiroki, Watanabe, Kentaro, Tanaka, Michinori, Ohno, Hiroaki, Izumi, Kazuki, Sakagami, Yasuko, Kodama, Eiichi, Matsuoka, Masao, Fujii, Nobutaka
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14-02-2008
• Subjects: Amino Acid Sequence; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Drug Resistance, Viral; HIV Envelope Protein gp41 - chemical synthesis; HIV Envelope Protein gp41 - chemistry; HIV Envelope Protein gp41 - pharmacology; HIV Fusion Inhibitors - chemical synthesis; HIV Fusion Inhibitors - chemistry; HIV Fusion Inhibitors - pharmacology; HIV-1 - drug effects; HIV-1 - physiology; Medical sciences; Molecular Sequence Data; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Protein Binding; Protein Structure, Secondary; Structure-Activity Relationship; Peptides; Molecular structure; HIV-1 virus; Retroviridae; Secondary structure; Lentivirus; Amphiphilic compound; In vitro; Biological activity; Virus; Biological fixation; Enfuvirtide; Polypeptide; Antiviral; Inhibitor; Helical structure; Human immunodeficiency virus; Chemical synthesis
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm701109d

Reported herein are the design, biological activities, and biophysical properties of a novel HIV-1 membrane fusion inhibitor. α-Helix-inducible X-EE-XX-KK motifs were applied to design an enfuvirtide analogue 2 that exhibited highly potent anti-HIV activity against wild-type HIV-1, enfuvirtide-resistant HIV-1 strains, and an HIV-2 strain in vitro. Indispensable residues for bioactivity of enfuvirtide, including the residues interacting with the N-terminal heptad repeat and the C-terminal hydrophobic residues, were identified.