Facile incorporation of urea pseudopeptides into protease substrate analogue inhibitors

被引：42

作者：

Myers, AC ^{[1
]}

Kowalski, JA ^{[1
]}

Lipton, MA ^{[1
]}

机构：

[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 20期

关键词：

peptide analogue protease inhibitor;

D O I：

10.1016/j.bmcl.2004.07.092

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new procedure that employs a one-pot, oxidative Hofmann rearrangement to incorporate a urea linkage into peptide backbones is detailed herein. This methodology was used to replace the scissile peptide bonds of [Leu(5)]enkephalin and a hexapeptide HIV-1 protease substrate. The [Leu(5)]enkephalin analogue was found to inhibit cleavage of hippurylhistidylleucine (HHL) by porcine kidney angiotensin-converting enzyme (PK-ACE) with a 0.88 mM IC50 value, comparable to the Michaelis constant of [Leu(5)]enkephalin with the same enzyme. The HIV-1 protease substrate analogue was shown to inhibit HIV-1 protease with an IC50 = 34muM. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5219 / 5222

页数：4

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