PAR2-AP衍生的拟肽作为激肽释放酶5和6抑制剂的合成、生物学评价及对接研究

Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6.

作者信息

Severino Beatrice, Fiorino Ferdinando, Corvino Angela, Caliendo Giuseppe, Santagada Vincenzo, Assis Diego Magno, Oliveira Juliana R, Juliano Luiz, Manganelli Serena, Benfenati Emilio, Frecentese Francesco, Perissutti Elisa, Juliano Maria Aparecida

出版信息

Biol Chem. 2015 Jan;396(1):45-52. doi: 10.1515/hsz-2014-0190.

DOI:10.1515/hsz-2014-0190

PMID:25153237

Abstract

A series of protease activated receptor 2 activating peptide (PAR2-AP) derivatives (1-15) were designed and synthesized. The obtained compounds were tested on a panel of human kallikreins (hKLK1, hKLK2, hKLK5, hKLK6, and hKLK7) and were found completely inactive toward hKLK1, hKLK2, and hKLK7. Aiming to investigate the mode of interaction between the most interesting compounds and the selected hKLKs, docking studies were performed. The described compounds distinguish the different human tissue kallikreins with compounds 1 and 5 as the best hKLK5 and hKLK6 inhibitors, respectively.

摘要

设计并合成了一系列蛋白酶激活受体2激活肽（PAR2-AP）衍生物（1-15）。对所得到的化合物在一组人激肽释放酶（hKLK1、hKLK2、hKLK5、hKLK6和hKLK7）上进行了测试，发现它们对hKLK1、hKLK2和hKLK7完全无活性。为了研究最具吸引力的化合物与所选hKLKs之间的相互作用模式，进行了对接研究。所描述的化合物能够区分不同的人组织激肽释放酶，化合物1和5分别是hKLK5和hKLK6的最佳抑制剂。