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

The Journal of Antibiotics
1991.0

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, carbohydrate utilization and other diagnostic tests indicated that this culture was a unique strain of Streptomyces. A complete summary of culture characteristics is available upon request from the authors.

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