Multiresidue Tetrapeptide Substitutions Yield a 140-fold Selective Melanocortin-3 over Melanocortin-4 Receptor Agonist.

ABSTRACT: The five melanocortin receptors regulate numerous physiological functions. Although many ligands have been developed for the melanocortin-4 receptor (MC4R), the melanocortin-3 receptor (MC3R) has been less-well characterized, in part due to the lack of potent, selective tool compounds. Previously an Ac-His-Arg-(pI)DPhe-Tic-NH₂ scaffold, inverting the Phe-Arg motif of the native melanocortin signal sequence, was identified to possess mMC3R over mMC4R selective agonist activity. In this study, a library of 12 compounds derived from this scaffold was synthesized and assayed at the mouse melanocortin receptors (MCRs), utilizing substitutions previously shown to increase mMC3R agonist potency and/or selectivity. One compound (8, Ac-Val-Gln-DBip-DTic-NH₂) was identif

SUBMITTER: Ericson MD 

PROVIDER: S-EPMC7812669 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature