Amastatin and Analogs

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.