Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH2 at the human melanocortin-1 and-4 receptors:: Histidine substitution

被引：24

作者：

Cheung, AWH ^{[1
]}

Danho, W ^{[1
]}

Swistok, J ^{[1
]}

Qi, LD ^{[1
]}

Kurylko, G ^{[1
]}

Rowan, K ^{[1
]}

Yeon, M ^{[1
]}

Franco, L ^{[1
]}

Chu, XJ ^{[1
]}

Chen, L ^{[1
]}

Yagaloff, K ^{[1
]}

机构：

[1] Hoffmann La Roche Inc, Roche Res Ctr, Nutley, NJ 07110 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 01期

关键词：

D O I：

10.1016/S0960-894X(02)00830-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Systematic substitution of His(6) residue using non-selective hMC4R pentapeptide agonist (Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)- NH2) as the template led to the identification of Bu-Atc(6)(2-aminotetraline-2-carboxylic acid)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH2 which showed moderate selectivity towards hMC4R over hMC1R. Further SAR studies resulted in the discovery of Penta-5-BrAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH2 and Penta-5-Me(2)NMAtc(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH2 which are potent hMC4R agonists and are inactive in hMC1R, hMC3R and hMC5R agonist assays. (C) 2002 Published by Elsevier Science Ltd.

引用

页码：133 / 137

页数：5

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