Chloropeptins, New Anti-HIV Antibiotics Inhibiting gp120-CD4 Binding from Streptomyces sp. II. Structure Elucidation of Chloropeptin I.

Abstract

The structure of chloropeptin I, a gpl20-CD4 binding inhibitor having a potent anti-HIV activity, was elucidated by XHand 13C NMRexperiments and chemical degradation. It is a peptide antibiotic consisting of six aryl amino acids residues and an a-oxo aryl acid some of which have chlorine atoms. Chloropeptins I (1) and II (2) are peptide antibiotics isolated from a culture broth of Streptomyces sp. WK-3419 as potent inhibitors against gpl20-CD4 binding1'2*. They inhibit strongly both the cytopathic effect assayed in HIV-1-infected MT-4 cells and the syncytium formation in co-cultured HIV-1-infected and uninfected MOLT-4cells2). 1 is a new compound although 2 was identified with complestatin3) which has been reported to inhibit the hemolysis of erythrocytes sensitized by the complementsystem4*. In this paper, we wish to report the structure of 1, elucidated via combination of NMR analysis and chemical degradation. Results and Discussion

Crystal Structure of Methyl (8R,11R,14S)-8-[N-[(tert-Butoxy)carbonyl]amino]-11-(3,5-dichloro-4-hydroxyphenyl)-18,19-dibromo-5-iodo-4-hydroxy-13-methyl-9,12-dioxo-10,13-diaza-2-oxatricyclo[14.2.2.13,7]heneicosa-3,5,7(21), 16,18,19-hexaene-14-carboxylate

“…2, the title compound was found to be a trans isomer of the N-methylamide bond in the solid state, because the torsion angles of C11A-N1A-C12A-O4A and C11B-N1B-C12B-O4B were 178å nd -176˚, respectively. The absolute configuration of the left-hand segment of chloropeptin proposed by Hirono et al 2,3 was finally supported by this X-ray analysis through a refinement of the inverted configuration (R = 0.095, Rw = 0.232).…”

Natural Products from Actinobacteria Associated with Fungus-Growing Termites

“…First, it contains a 2,3-dehydro-2-aminobutyric acid (Dhb), which presumably originates from the dehydration of threonine [ 53 ], and is frequently found in bioactive natural products family like nonribosomal peptides [ 54 ] and lanthipeptides [ 55 ]. Secondly, it contains a 3,5-dichlorotyrosine moiety, which is a building block of several natural products like chloropeptin [ 56 ] from Streptomyces lavendulae , and cyclo(13,15-dichloro-L-Pro-L-Tyr) from fungi Leptoxyphium sp. In addition, the modified amino acid has been detected in cuticles from several insect species, where they might play important roles in the sclerotization process [ 57 ].…”

Complestatin Exerts Antibacterial Activity by the Inhibition of Fatty Acid Synthesis

“…9) Chloropeptin I and neuroprotectins have been coisolated in the complestatin-producing Streptomyces, 9,10) suggesting that 2 and 3 may be chloropeptin I or neuroprotectins. Indeed, the 1 H-NMR data of 2 and 3 were almost the same as those of neuroprotectin A 11) and chloropeptin I, 17) respectively, in the literatures. The 13 C-NMR data of 2 and 3 were also similar with those of neuroprotectin A and chloropeptin I although the complete 13 C-NMR data of 2 and 3 were not obtained due to their tiny amount.…”