FR901724, a novel anti-human immunodeficiency virus (HIV) peptide produced by Streptomyces, shows synergistic antiviral activities with HIV protease inhibitor and 2',3'-dideoxynucleosides.
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.
Nakashima
H
H
Department of Microbiology, Yamanashi Medical University, Japan.
Ichiyama
K
K
Inazawa
K
K
Ito
M
M
Hayashi
H
H
Nishihara
Y
Y
Tsujii
E
E
Kino
T
T
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004357:Drug Synergism; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology; D013302:Streptomyces / Q000378:metabolism*; D019065:Virus Assembly / Q000187:drug effects
D000998:Antiviral Agents; D015224:Dideoxynucleosides; C101430:FR 901724; D017320:HIV Protease Inhibitors; D010456:Peptides, Cyclic; D011134:Polysaccharides