Chloropeptins, New Anti-HIV Antibiotics Inhibiting gp120-CD4 Binding from Streptomyces sp.

I. Taxonomy, Fermentation, Isolation, and Physico-chemical Properties and Biological Activities

Abstract

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 pep tides. 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 μM, respectively), the cytopathic effect of HIV in MT-4 cells (EC₅₀: 1.6 and 1.7 μM, respectively) and syncytium formation in co-cultured HIV-1-infected and uninfected MOLT-4 cells (IC₅₀: 0.5 and 1.1 μM, respectively). Chloropeptin I was synergistic in the inhibition of the cytopathic effect when combined with other anti-HIV drugs such as zidovudine (AZT), didanosine (ddl), zalcitabine (ddC) and nevirapine.