Structural Insights into Selective Ligand-Receptor Interactions Leading to Receptor Inactivation Utilizing Selective Melanocortin 3 Receptor Antagonists.

ABSTRACT: Systematic N-methylated derivatives of the melanocortin receptor ligand, SHU9119, lead to multiple binding and functional selectivity toward melanocortin receptors. However, the relationship between N-methylation-induced conformational changes in the peptide backbone and side chains and melanocortin receptor selectivity is still unknown. We conducted comprehensive conformational studies in solution of two selective antagonists of the third isoform of the melanocortin receptor (hMC3R), namely, Ac-Nle-c[Asp-NMe-His⁶-d-Nal(2')⁷-NMe-Arg⁸-Trp⁹-Lys]-NH₂ (15) and Ac-Nle-c[Asp-His⁶-d-Nal(2')⁷-NMe-Arg⁸-NMe-Trp⁹-NMe-Lys]-NH₂ (17). It is known that the pharmacophore (His⁶-DNal

SUBMITTER: Cai M 

PROVIDER: S-EPMC5999403 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature