Structure-activity relationship study between Ornithyl-Proline and Lysyl-Proline based tripeptidomimics as angiotensin-converting enzyme inhibitors

被引：14

作者：

Pavar, MC

Hanif, K

Azam, A

Lata, S

Pasha, MAQ

Pasha, S

机构：

[1] Inst Genom & Integrat Biol, Peptide Synth Lab, Delhi 110007, India

[2] Jamia Millia Islamia, Dept Chem, New Delhi 110025, India

[3] Inst Genom & Integrat Biol, Funct Genom Unit, Delhi 110007, India

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 08期

关键词：

ACE inhibitors; tripeptidomimics; unnatural amino acids; carboxylic acid derived heterocyclics;

D O I：

10.1016/j.bmcl.2006.01.061

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A designed library of tripeptidomimics of Ornithyl-Proline (Orn-Pro) and Lysyl-Proline (Lys-Pro) conjugated with various unnatural amino acids and carboxylic acid derived heterocyclics was synthesized and screened for possible inhibitors of angiotensin-converting enzyme (ACE). Among the tripeptidomimics 10[MTP-Orn-Pro], 11[HTP-Orn-Pro], 14[TA-Orn-Pro] and 20[BPA-Orn-Pro] showed prominent inhibition with IC50 values in micromolar concentrations. Structure-activity relationship study indicated that C-3 side chain of Orn as compared to C-4 side chain of Lys at P-1, position was better suited to inhibit ACE, with propionic acid (C-3) derived heterocyclics and unnatural amino acids. (C) 2006 Elsevier Ltd. All rights reserved.

引用

页码：2117 / 2121

页数：5

共 27 条

[1] ACE revisited: A new target for structure-based drug design [J].