FR901724, a Novel Anti-human Immunodeficiency Virus (HIV) Peptide Produced by Streptomyces, Shows Synergistic Antiviral Activities with HIV Protease Inhibitor and 2', 3'-Dideoxynucleosides

• Published in: Biological & pharmaceutical bulletin Vol. 19; no. 3; pp. 405 - 412
• Main Authors: NAKASHIMA, Hideki, ICHIYAMA, Kohji, INAZAWA, Kazuhiko, ITO, Masahiko, HAYASHI, Hideya, NISHIHARA, Yutaka, TSUJII, Eisaku, KINO, Toru
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01-03-1996; Maruzen; Japan Science and Technology Agency
• Subjects: AIDS; Amino Acid Sequence; anti-HIV compound; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Biological and medical sciences; Blotting, Western; Cytopathogenic Effect, Viral - drug effects; dideoxynucleoside; Dideoxynucleosides - pharmacology; drug combination; Drug Synergism; HIV Protease Inhibitors - pharmacology; human immunodeficiency virus; Humans; Medical sciences; Molecular Sequence Data; Peptides, Cyclic - metabolism; Peptides, Cyclic - pharmacology; Pharmacology. Drug treatments; Polysaccharides - pharmacology; protease inhibitor; Streptomyces; Streptomyces - metabolism; Virus Assembly - drug effects; Cell culture; Drug combination; Streptomycetaceae; Peptides; Enzyme; Retroviridae; Enzyme inhibitor; Streptomyces; Tricyclic compound; In vitro; Actinomycetales; Virus; Microbial origin; Analog; Nucleotide; Bacteria; Hydrolases; Lentivirinae; Antiviral; Actinomycetes; Human immunodeficiency virus; Mechanism of action; Proteinases
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.19.405

A novel tricyclic 21-amino-acid peptide, FR901724, was isolated from the cultured broth of Streptomyces sp. No. 73264. This peptide appears to possess potent anti-human immunodeficiency virus (HIV) activity in vitro and might represent a lead to a new class of anti-HIV agents ; it qualifies as an HIV-cell fusion inhibitor because of its weak inhibition of virus-cell binding and strong inhibition of syncytium formation. From the time-of-addition experiments, the mode of action of FR901724 was found to definitely differ from that of KNI-272, a peptide mimetic allophenylnorstatine-derivative HIV protease inhibitor. FR901724 appears to interact with a stage of the virus replicative cycle that may well correspond to virus-cell fusion. We also found that FR901724 was synergistic or had a strong tendency toward synergism when combined with other antiviral drugs, such as KNI-272, AZT, ddI and dextran sulfate.