L-156,602, a C5a antagonist with a novel cyclic hexadepsipeptide structure from Streptomyces sp. MA6348. Fermentation, isolation and structure determination.

Abstract

The recently discovered class of cyclic hexadepsipeptide antibiotics is exemplified by azinothricin1) and A83586C2). In our search for novel substances with C5a antagonistic properties, a member of this class, L-156,602, was isolated from a newly isolated strain of streptomycete and found to be a competitive inhibitor of the binding of the anaphylatoxin C5a to its receptor on human PMNs3). Because of its broad range of biological properties, C5a has been implicated as a causative or aggravating agent in a variety of inflammatory and allergic diseases4'5) and an inhibitor of such inflammatory actions would therefore be therapeutically beneficial in the treatment of such diseases. The producing organism, MA-6348, was isolated from a plant rhizosphere soil sample obtained from a Japanese garden. Comparison of spectral data suggested the compound to be identical to PD 124,966, but no structure has been published6'7). We report here primarily on the structure determination of L-156,602 including absolute stereochemistry, based on spectroscopic and X-ray diffraction analyses. The culture was characterized by the International Streptomyces Project procedures described by Shirling and Gottlieb8*. Pigment production,

International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors

“…The hexadepsipeptide L156,602 (Fig. 5D) is a nonselective antibiotic antagonist for the C5a 1 receptor from Streptomyces with a pIC 50 = 5.7 at the C5a 1 receptor, although extensive modification failed to improve selectivity (Hensens et al, 1991;Tsuji et al, 1992aTsuji et al, ,b, 1995. The C terminus of C5a has also been exploited by the use of phage display to allow selection of libraries of C5a mutants to produce a potent antagonist, A8 D71-73 (Heller et al, 1999).…”

A new 16-membered tetraene macrolide JBIR-100 from a newly identified Streptomyces species

“…antitumor [368][369][370] , tuberculostatics [371] , anti-inflammatory [372] and anti-HIV agents [373,374] . Monamycin, a series of antibiotics [16] , containing piperazic acids have been isolated from the culture broth of numerous Streptomyces spp.…”

Electrospray Ionization Mass Spectra of Piperazimycins A and B and γ-Butyrolactones from a Marine-derived Streptomyces sp.†

“…[6]. They are known for their antitumor [7ϳ9], tuberculostatic [10], anti-inflammatory [11], and anti-HIV activity [12,13] and are chemically characterized by further rare amino acids, like diaminobutyric acid, dehydroamino acids, p-dimethylaminophenylalanine etc. [14].…”