Structure–activity relationship of linear tetrapeptides Tic-DPhe-Arg-Trp-NH2 at the human melanocortin-4 receptor and effects on feeding behaviors in rat
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- 作者：Zhixiong Ye ; Tanya MacNeil ; David H. Weinberg ; Rubana N. Kalyani ; Rui Tang ; Alison M. Strack ; Beth A. Murphy ; Ralph T. Mosley ; D. Euan MacIntyre ; Lex H.T. Van der Ploeg et al.
- 关键词：α ; -MSH ; Melanocortin ; MC4R ; Agonist ; Tetrapeptide ; Food intake
- 刊名：Peptides
- 出版年：2005
- 出版时间：2005
- 年：2005
- 卷：26
- 期：10
- 页码：2017-2025
- 全文大小：364 K
文摘
The melanocortin subtype-4 receptor (MC4R) has been implicated in the control of feeding behavior and body weight regulation. A series of tetrapeptides, based on Tic-DPhe-Arg-Trp-NH2—a mimic of the putative message sequence “His-Phe-Arg-Trp” and modified at the DPhe position, were prepared and pharmacologically characterized for potency and selectivity. Substitution of His with Tic gave peptides with significant increases in selectivity. The effects of the substitution pattern of DPhe were investigated and it has significant influences on potency and the level of the maximum cAMP accumulation. Intracerebroventricular administration of peptide 10 induced significant inhibition of cumulative overnight food intake and feeding duration in rats.