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 mu M, respectively), the cytopathic effect of HIV in MT-4 cells (EC(50): 1.6 and 1.7 mu M, respectively) and syncytium formation in co-cultured HIV-l-infected and uninfected MOLT-4 cells (IC50: 0.5 and 1.1 mu M, 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.