Isolation and characterization of elasnin, a new human granulocyte elastase inhibitor produced by a strain of Streptomyces.

The Journal of Antibiotics
1978.0

Abstract

In the course of a screening program for useful inhibitors against human granulocyte elastase, a new elastase inhibitor "elasnin" was found in the culture filtrates of Streptomyces noboritoensis KM-2753. The present paper deals with taxonomic studies of the producing strain, fermentation, isolation, and characterization of elasnin, and this culture also produced anti-candida activity. Elasnin was isolated from the fermentation broth by column chromatography on silica gel and neutral alumina. It is a neutral, colorless, and viscous oil with a refractive index (n;;) of 1.4983, a specific rotation ([a];') of -0.9° (c 1.0, ethanol), and an ultraviolet (UV) absorption maximum at 291 nm (molar extinction coefficient ε 7,760 in ethanol). Its molecular formula was determined to be C24H40O4 (molecular weight 392) via elemental analysis and mass spectrometry. Elasnin markedly inhibits human granulocyte elastase but shows almost no activity against pancreatic elastase, chymotrypsin, and trypsin. The 50% inhibitory concentration (IC50) for human elastase is 1.3 pg/ml (3.3×10^-6 M), whereas the IC50 for pancreatic elastase is 30.1 pg/ml (76.8×10^-6 M).

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