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The melanocortins are a group of structurally related peptides derived from proopiomelanocortin (POMC), their name from their melanotropic and corticotropic activities and are comprised of adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone (α-MSH), β-MSH, and γ-MSH. The effects of melanocortins are mediated by activation of a family of melanocortin receptors (MCRs). Five MCR (MC1R, MC2R, MC3R, MC4R, and MC5R) (Figure 2) genes have been cloned and the receptors pharmacologically characterized [1]. All the melanocortin ligands conserve the core sequence, Trp-Arg-Phe-His. Previous SAR study on melanotropins, in particular on α-MSH, led to the small cyclic peptide MT-II, a potent and non-selective agonist at MCRs.

Novel Macrocyclic Peptides Active at Human Melanocortin Receptors: A Preliminary SAR Study