Melanocortin & Kisspeptin Receptor Ligands

The five melanocortin receptors are class A GPCRs coupled to Gs; they bind fragments of pro-opiomelanocortin such as alpha-MSH and differ in tissue distribution and ligand selectivity. The kisspeptin receptor (KISS1R, formerly GPR54) is a Gq-coupled GPCR whose endogenous ligands are kisspeptins, products of the KISS1 gene sharing a common C-terminal decapeptide.

Melanotan I (afamelanotide) is a linear alpha-MSH analogue with norleucine at position 4 and D-phenylalanine at position 7. Melanotan II is a cyclic lactam heptapeptide, a non-selective agonist across MC1R, MC3R, MC4R and MC5R. PT-141 (bremelanotide) is a metabolite of Melanotan II that lacks the C-terminal amide, with altered subtype selectivity. Kisspeptin-10 is the shortest fully active kisspeptin fragment.

Identity is established by mass spectrometry: an intact mass, or a precursor and fragment transition (MRM) matched against a reference standard, confirms that the sequence in the vial is the one on the label. Purity is a chromatographic figure, the principal peak area by reversed-phase HPLC, and it bounds peptide-related impurities only; it says nothing about counterion, water or residual solvent content, which is why net peptide content is reported separately. Lyophilised material is stored cold, dry and dark, and a certificate states what was measured on one named lot. For cyclic peptides such as Melanotan II and PT-141 the intact mass confirms ring closure, since the linear precursor differs by the mass of water, and the two compounds differ from each other by the C-terminal amide, a 1 Da difference that needs adequate mass resolution to see.

In vitro work measures receptor binding by radioligand displacement and activation by cAMP accumulation (melanocortin receptors) or calcium and IP-1 signalling (KISS1R), in cell lines expressing a single receptor subtype. Selectivity figures depend heavily on the assay and receptor species, so compare values from the same system. Clinical literature on the approved members of these classes reports organism outcomes and is outside the scope of a research-use reference.