Definition

Amastatin is a oligopeptide antibiotic complex that is a competitive inhibitor of aminopeptidases and also has antitumor property.

Discovery

Amastatin was isolated from the culture filtrate of Streptomyces spME98-M3¹.

Analog of Amastatin

Epiamastatin is a diastereoepimer of the effective peptidase inhibitor amastatin and differs structurally by a single transposition of the OH group with H atom at C₂. Compared with amastatin, epiamastatin is pharmacologically inactive.

Structure

The structure of amastatin is (2S, 3R)-3-Amino-2-hydroxy-5-methyl-hexanoyl]-Val-Val-Asp. There are three kinds of functional group NH2, OH and COOH, in the amastatin molecule.

Functions

It is a competitive inhibitor of the aminopeptidases A and M². It inhibits cytosolic leucine aminopeptidase, microsomal aminopeptidase M and bacterial leucine aminopeptidase³.

References

1.     Tobe H, Morishima H, Aoyagi T, Umezawa H,  Isshiki K, Nakamura K, Yoshioka T, Shimauchi Y, Inui T. (!982). Synthesis and structure-activity relationships of amastatin analogues, inhibitors of aminopeptidase A. Agric. Biol. Chem., 46:1865-1872.

2.     Rich DH, Moon BJ, Harbeson S (1984). Inhibition of aminopeptidases by amastatin and bestatin derivatives. Effect of inhibitor structure on slow-binding processes.  J Med Chem., 27(4):417-22.

3.     Wilkes SH, Prescott JM. (1985). The slow, tight binding of bestatin and amastatin to aminopeptidases. J Biol Chem., 260(24):13154-62.