Structure-activity relationship of linear tetrapeptides Tic-DPhe-Arg-Trp-NH2 at the human melanocortin-4 receptor and effects on feeding behaviors in rat

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...

Full description

Saved in:
Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2005-10, Vol.26 (10), p.2017-2025
Main Authors: Ye, Zhixiong, MacNeil, Tanya, Weinberg, David H, Kalyani, Rubana N, Tang, Rui, Strack, Alison M, Murphy, Beth A, Mosley, Ralph T, Euan MacIntyre, D, Van der Ploeg, Lex H T, Patchett, Arthur A, Wyvratt, Matthew J, Nargund, Ravi P
Format: Article
Language:English
Subjects:
Animals
Appetite Depressants - administration & dosage
Appetite Depressants - chemical synthesis
Appetite Depressants - metabolism
Binding, Competitive
CHO Cells
Cricetinae
Cricetulus
Eating - drug effects
Eating - physiology
Humans
Male
Models, Molecular
Oligopeptides - administration & dosage
Oligopeptides - chemical synthesis
Oligopeptides - metabolism
Rats
Rats, Sprague-Dawley
Receptor, Melanocortin, Type 4 - metabolism
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0196-9781
DOI:10.1016/j.peptides.2004.12.035