Synthesis and biological activity of novel peptide mimetics as melanocortin receptor agonists

A series of novel peptidomimetic analogs was prepared containing cyclohexyl, phenyl, or heterocyclic groups to ostensibly orient the guanidine or mimic of an arginine in a putative melanocortin receptor ligand pharmacophore. Some binding affinity at the melanocortin receptors MC3 and MC4 was noted. In silico docking also indicated that the relative positions of the hydrogen-bonding sites and hydrophobic regions of the compounds are reasonably well matched to the receptor-binding site. This may present a lead entry into a selective series of MC4R agonists.

Graphical abstractThe design, synthesis, and biological activity of a series of peptidomimetic melanocortin receptor agonists is reported. Some binding affinity at the melanocortin receptors MC3 and MC4 was noted. In silico docking indicated that the relative positions of the hydrogen-bonding sites and hydrophobic regions of the compounds are reasonably well matched to the receptor-binding site. This may present a lead entry into a selective series of MC4R agonists.Figure optionsDownload full-size imageDownload as PowerPoint slide