Chloropeptins, new anti-HIV antibiotics inhibiting gp120-CD4 binding from Streptomyces sp. I. Taxonomy, fermentation, isolation, and physico-chemical properties and biological activities.
Chloropeptins I and II, which are gp120-CD4 binding inhibitors, were isolated as pale yellow-brown powders from the mycelia of a soil actinomycete, Streptomyces sp, WK-3419. Their physico-chemical properties showed that they are chlorinated peptides. Chloropeptin I (C61H45N7O15Cl6) is a novel compound, but chloropeptin II was identified as complestatin. Both compounds inhibited gp120-CD4 binding (IC50: 1.3 and 2.0 microM, respectively), the cytopathic effect of HIV in MT-4 cells (EC50: 1.6 and 1.7 microM, respectively) and syncytium formation in co-cultured HIV-1-infected and uninfected MOLT-4 cells (IC50. 0.5 and 1.1 microM, respectively). Chloropeptin I was synergistic in the inhibition of the cytopathic effect when combined with other anti-HIV drugs such as zidovudine (AZT), didanosine (ddI), zalcitabine (ddC) and nevirapine.
Tanaka
H
H
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Matsuzaki
K
K
Nakashima
H
H
Ogino
T
T
Matsumoto
A
A
Ikeda
H
H
Woodruff
H B
HB
Omura
S
S
D000900:Anti-Bacterial Agents / Q000302:isolation & purification* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000302:isolation & purification* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002733:Chlorophenols / Q000302:isolation & purification* / Q000494:pharmacology; D005285:Fermentation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009842:Oligopeptides / Q000302:isolation & purification* / Q000494:pharmacology; D010456:Peptides, Cyclic; D013302:Streptomyces / Q000145:classification / Q000378:metabolism*; D015215:Zidovudine / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D002733:Chlorophenols; D015699:HIV Envelope Protein gp120; D009842:Oligopeptides; D010456:Peptides, Cyclic; C090485:chloropeptin I; D015215:Zidovudine; C023490:complestatin