Discovery, purification and characterization of the angiotensin converting enzyme inhibitor, L-681,176, produced by Streptomyces sp. MA 5143a.

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Abstract
L-681,176, an inhibitor of angiotensin converting enzyme [a target for therapeutic treatment of essential hypertension], was found in the culture filtrate of Streptomyces sp. MA 5143. The I50 of the crystalline inhibitor is about 1.3 .mu.g/ml and the inhibition is reversed by ZnSO4. In rats, L-168,176 exhibits a dose-related inhibition of the pressor response to angiotensin I with an ID50 [median inhibitory dose] of 142 mg/kg when administered i.v. The structure of L-681,176 is similar to that of marasmine but lacking 1 carboxyl group. The maximum yield of L-681,176 occurs after 3-4 days growth at 28.degree. C.