Abstract
The Ac-His-DPhe-Arg-Trp-NH2 tetrapeptide is a nonselective melanocortin agonist and replacement of Arg in the tetrapeptide with acidic, basic or neutral amino acids results in reduced potency at the melanocortin receptor (MCR) isoforms (MC1R and MC3-5R). To determine the importance of the positive charge and the guanidine moiety for melanocortin activity, a series of urea- and thiourea-substituted tetrapeptides were designed. Replacement of Arg with Lys or ornithine reduced agonist activity at the mouse mMC1 and mMC3-5 receptors, thus supporting the hypothesis that the guanidine moiety is important for receptor potency, particularly at the MC3-5 receptors. The Arg side chain-modified tetrapeptides examined in this study include substituted phenyl, naphthyl, and aliphatic urea and thiourea residues using a Lys side-chain template. These ligands elicit full-agonist pharmacology at the mouse MCRs examined in this study.
Original language | English (US) |
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Pages (from-to) | 297-307 |
Number of pages | 11 |
Journal | Journal of Peptide Research |
Volume | 66 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2005 |
Keywords
- MC3R
- MC4R
- Melanocortin
- Melanotropin
- Obesity
- Tetrapeptide
- Thiourea
- Urea
- α-melanocyte-stimulating hormone
ASJC Scopus subject areas
- Biochemistry
- Endocrinology