Piperastatin A, A New Selective Serine Carboxypeptidase Inhibitor Produced by Actinomycete. I. Taxonomy, Production, Isolation and Biological Activities

Abstract

Piperastatin A (structure, N-formyl-allo IIe-Thr-Leu-Val-Pip-Leu-Pip, Pip = hexahydropyridadine-3-carboxylic acid; molecular weight, 809), a new inhibitor of serine carboxypeptidase was discovered in the fermentation broth of Streptomyces lavendofoliae MJ908-WF13. It was purified by activated charcoal chromatography, YMC gel ODS-A chromatograpy and centrifugal partition chromatography (CPC) by monitoring its inhibitory activity against carboxypeptidase Y (CP-Y), and finally obtained as colourless needles. Piperastatin A is a competitive inhibitor of the enzyme with K_i = 52° 6.2 nM. Piperastatin A is a highly specific inhibitor of the serine carboxypeptidases, CP-Y and platelet deamidase with little effect on related enzymes, has no antimicrobial activity and has low toxicity.

Key Words: :

• Serine carboxypeptidase
• carboxypeptidase Y
• enzyme inhibitor
• peptide
• Actinomycete
• natural compound