Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH2 at the human melanocortin-1 and-4 receptors:: Histidine substitution
Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH2 at the human melanocortin-1 and-4 receptors:: Histidine substitution
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DOI：
10.1016/s0960-894x(02)00830-2
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发表时间：
2003-01-06
影响因子：
2.7
通讯作者：
Yagaloff, K
中科院分区：
文献类型：
--
作者：
Cheung, AWH;Danho, W;Yagaloff, K
使用非选择性hMC 4 R五肽激动剂（Bu-His（6）-DPhe（7）-Arg（8）-Trp（9）-Gly（10）-NH 2）作为模板对His（6）残基进行系统性取代，鉴定出Bu-Atc（6）（2-氨基四氢萘-2-羧酸）-DPhe（7）-Arg（8）-Trp（9）-Gly（10）-NH 2，其显示出相对于hMC 1 R对hMC 4 R的中等选择性。进一步的SAR研究发现了Penta-5-BrAtc（6）-DPhe（7）-Arg（8）-Trp（9）-Gly（10）-NH 2和Penta-5-Me（2）NMAtc（6）-DPhe（7）-Arg（8）-Trp（9）-Gly（10）-NH 2，它们是有效的hMC 4 R激动剂，在hMC 1 R、hMC 3R和hMC 5 R激动剂试验中无活性。(C)2002年由Elsevier Science Ltd.出版
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.