Maduropeptin, a complexof newmacromolecular antitumor antibiotics, is a metabolite of Actinomadura madurae H710-49. The active components maduropeptins A1? A2 and B are acidic chromopeptides with MWof around 22,500 and composed of 14 types of amino acids and an unstable chromophore. The antibiotics are active in vitro against Gram-positive bacteria and highly cytotoxic to tumor cells. They produced significant prolongation of survival time of mice implanted with P388 leukemia and B16 melanoma. 403 In the course of screening for novel metabolites active against murine P388 leukemia in mice, we found a complexof newmacromolecularantibiotics designated maduropeptin. The producing culture H710-49, isolated from a soil sample collected in Germany, was identified as Actinomadura madurae (ATCC39144). Maduropeptin is an acidic macromolecular substance from its extraction behavior; the active principle was recovered from the fermentation broth by use of a basic ion exchange resin. HPLC analysis indicated that the crude solid contained at least four active components (maduropeptins Al9 A2, B and D) and an inactive component (maduropeptin C) having similar physico-chemical properties. Upon UVirradiation in a cold room, components B and D were decomposed yielding a complex of components A1? A2 and C which were isolated as single entities by chromatography. The bioactive maduropeptin components showed MW'saround 22,500 and characteristic UVabsorption maximaat 210, 286 and 308 nm. They exhibited potent inhibitory activity against Gram-positive bacteria and tumor cells and strong in vivo antitumor effect against P388 leukemia and B16 melanomaimplanted in mice. In this paper, we report the producing organism, production, isolation, chemical properties and biological activities of maduropeptin. Producing OrganismAn actinomycete strain, No. H710-49 (ATCC39144), was isolated from a soil sample collected in Germany. Strain H710-49 forms both substrate and aerial mycelia. The substrate mycelium is long, branched and not fragmented into short filaments. Short spore-chains are born on the tip or monopodial branch of the aerial mycelium. The spore-chains contain 2~15 spores (mostly 4~8 spores), per chain, and are straight, hooked or spiral in shape. The spores are oval to elliptical (0.5~0.6 x 0.7~1.2 urn) with Maduropeptin was originally called as BBM-1644.
The structures of Bu-2470A, B1, B2a, and B2b have been determined. Bu-2470A is a simple octapeptide having no fatty acid moiety, while Bu-2470 B1, B2a and B2b are octapeptides that have been acylated with a ;3-hydroxy C11 or C10 fatty acid. The octapeptide structure of Bu-2470 components was found identical with that of octapeptin C1, hence generic names of octapeptin C0, C2 C3 and C4 are proposed for Bu-2470 A, B1, B2, and B2b, respectively. Bu-2470 is a new peptide antibiotic complex produced by a strain of Bacillus circulars. The producing organism, fermentation, isolation and properties of Bu-2470 A, B1 and B2 have been reported1). This paper describes the structure determination of Bu-2470 A, B1, B2a and B2b. Constituent Amino Acids of Bu-2470 A The amino acid analysis of the acid hydrolysate of Bu-2470 A indicated the presence of phenylalanine (Phe), leucine (Leu) and a,r-diaminobutyric acid (Dab) with a molar ratio of 1: 2: 5. The spe
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