哌拉他汀A，一种由放线菌产生的新型选择性丝氨酸羧肽酶抑制剂。I. 分类学、生产、分离及生物学活性

Piperastatin A, a new selective serine carboxypeptidase inhibitor produced by actinomycete. I. Taxonomy, production, isolation and biological activities.

作者信息

Murakami S, Harada S, Yamazaki T, Takahashi Y, Hamada M, Takeuchi T, Aoyagi T

机构信息

Institute of Microbial Chemistry, Tokyo, Japan.

出版信息

J Enzyme Inhib. 1996;10(2):93-103. doi: 10.3109/14756369609020162.

DOI:10.3109/14756369609020162

PMID:8835934

Abstract

Piperastatin A (structure, N-formyl-allo Ile-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 chromatography 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 Ki = 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.

摘要

哌拉他汀A（结构为N-甲酰基-别异亮氨酸-苏氨酸-亮氨酸-缬氨酸-哌啶酸-亮氨酸-哌啶酸，哌啶酸=六氢吡啶-3-羧酸；分子量809）是在淡紫链霉菌MJ908-WF13发酵液中发现的一种新型丝氨酸羧肽酶抑制剂。通过监测其对羧肽酶Y（CP-Y）的抑制活性，经活性炭色谱、YMC凝胶ODS-A色谱和离心分配色谱（CPC）进行纯化，最终得到无色针状晶体。哌拉他汀A是该酶的竞争性抑制剂，其抑制常数Ki = 52±6.2 nM。哌拉他汀A是丝氨酸羧肽酶CP-Y和血小板脱酰胺酶的高度特异性抑制剂，对相关酶影响很小，无抗菌活性且毒性低。