Amastatin (hydrochloride)

Amastatin (hydrochloride) is a competitive inhibitor of various aminopeptidases with slow but strong binding (Ki = 0.26, 30 and 52 nM for Aeromonas aminopeptidase, cytosolic leucine aminopeptidase and microsomal aminopeptidase) [1].

Aminopeptidases, found in many subcellular organelles, in cytosol, and as membrane components, are enzymes that catalyze the cleavage of amino acids from the amino of proteins or peptides. Aminopeptidases play important roles in various essential cellular functions [1].

Amastatin (10 μg/ml ~ 1 mg/ml) exhibited dose-dependent inhibitory profiles on E. cuniczcli replication in vitro [2]. In addition, in spleen lymphocyte cultures with macrophages, Amastatin stimulated [³H]thymidine incorporation into lymphocytes/macrophages, with the optimal stimulatory concentration around 0.1 μg/ml [3].

In anesthesized rats, infusion of amastatin (16 nmol/min i.v.) only slightly increased the potency of angiotensin I and AII, whilst significantly increased the potency of AIII and des(Asp1)angiotensin I. Furthermore, amastatin specifically inhibited plasma aminopeptidase M and aminopeptidase A activities by 81% and 10%, respectively [4].

References:

[1]. Wilkes S H, Prescott J M. The slow, tight binding of bestatin and amastatin to aminopeptidases. Journal of Biological Chemistry, 1985, 260(24): 13154-13162.

[2]. Millership J J, Didier E S, Okhuysen P C, et al. In vitro and in vivo evaluation of aminopeptidase inhibitors as antimicrosporidial therapies. Journal of Eukaryotic Microbiology, 2001, Suppl: 95S-98S.

[3]. Weissmann N, Leyhausen G, Maidhof A, et al. Mitogenic potentials of bestatin, amastatin, arphamenines A and B, FK-156 and FK-565 on spleen lymphocytes. The Journal of Antibiotics, 1985, 38(6): 772-778.

[4]. Ahmad S, Ward P E. Role of aminopeptidase activity in the regulation of the pressor activity of circulating angiotensins. Journal of Pharmacology and Experimental Therapeutics, 1990, 252(2): 643-650.