Preparation of human melanocortin-4 receptor agonist libraries:: Linear peptides X-Y-DPhe7-Arg8-Trp(or 2-Nal)9-Z-NH2

被引：9

作者：

Cheung, AWH ^{[1
]}

Qi, LD ^{[1
]}

Gore, V ^{[1
]}

Chu, XJ ^{[1
]}

Bartkovitz, D ^{[1
]}

Kurylko, G ^{[1
]}

Swistok, J ^{[1
]}

Danho, W ^{[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 | 2005年 / 15卷 / 24期

关键词：

melanocortin receptors; peptides; agonist;

D O I：

10.1016/j.bmcl.2005.08.083

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two libraries of hMC4R agonists, X-Y-DPhe(7)-Arg(8)-2-Nal(9)-Z-NH2 and X-Y-DPhe(7)-Arg(8)-Trp(9)-Z-NH2, totaling 185 peptides were 6 prepared using Irori radiofrequency tagging technology and Argonaut Quest 210 Synthesizer, where X stands for N-caps, Y for His(6) surrogates and Z for Gly(10) surrogates. As a result of this study, His-modified pentapeptides with Trp were found to be more hMC4R potent than the corresponding 2-Nal analogs, novel N-caps and Gly surrogates were identified and 19 new peptides which are potent hMC4R agonists (EC50 1-15 nM) and selective against hMC1R were discovered. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：5504 / 5508

页数：5

共 13 条

[1] A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences [J].

Benoit, SC ;

Schwartz, MW ;

Lachey, JL ;

Hagan, MM ;

Rushing, PA ;

Blake, KA ;

Yagaloff, KA ;

Kurylko, G ;

Franco, L ;

Danhoo, W ;

Seeley, RJ .

JOURNAL OF NEUROSCIENCE, 2000, 20 (09) :3442-3448

[2]

Boyce Rustum S, 2004, Curr Opin Investig Drugs, V5, P1063

[3]

Chen L., 2001, [No title captured], Patent No. [WO 01/74844, 2001-10-11, 0174844]

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

Cheung, AWH ;

Danho, W ;

Swistok, J ;

Qi, LD ;

Kurylko, G ;

Rowan, K ;

Yeon, M ;

Franco, L ;

Chu, XJ ;

Chen, L ;

Yagaloff, K .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (01) :133-137

[5] Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH2 at the human melanocortin-1 and-4 receptors:: Arginine substitution [J].

Cheung, AWH ;

Danho, W ;

Swistok, J ;

Qi, L ;

Kurylko, G ;

Franco, L ;

Yagaloff, K ;

Chen, L .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (17) :2407-2410

[6]

CHU XJ, IN PRESS BIOORG MED

[7]

CONE RD, 2000, MELANOCORTIN RECPTOR

[8] Structure-activity relationship of linear peptide Bu-His6-DPhe7-Arg8-Trp9-Gly10-NH2 at the human melanocortin-1 and-4 receptors:: DPhe7 and Trp9 substitution [J].

Danho, W ;

Swistok, J ;

Cheung, AWH ;

Kurylko, G ;

Franco, L ;

Chu, XJ ;

Chen, L ;

Yagaloff, K .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (04) :649-652

[9]

DANHO W, 2001, P 2 INT 17 AM PEPT S, P701

[10]

HOFMANNLAROCHE, 2002, Patent No. 0218437

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