Melanotan II: Structure and Melanocortin Receptor Research

30/09/2026 ·2 min di lettura · Ultima revisione 29/08/2026

Melanotan II is a cyclic seven-residue analogue of alpha-melanocyte-stimulating hormone, developed at the University of Arizona in the 1980s and 1990s as part of a programme to produce stable, potent melanocortin receptor ligands. It is one of the most-studied non-selective melanocortin agonists in the literature.

Structure

The sequence is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂. Four features distinguish it from the natural hormone:

• A lactam bridge between the aspartate side chain and the lysine side chain, cyclising the molecule. This locks the backbone into the conformation the receptor recognises, so the peptide does not pay an entropic cost to fold on binding.
• Norleucine replacing methionine at position 4 of the parent sequence — norleucine is isosteric with methionine but has no sulfur, so it cannot oxidise. This is a stability substitution.
• D-phenylalanine in place of L-phenylalanine, which both increases potency and resists proteolysis.
• N-terminal acetylation and C-terminal amidation, blocking exopeptidase attack at both ends.

Molecular formula C₅₀H₆₉N₁₅O₉, molecular weight approximately 1024.2 g/mol.

Receptor profile

The defining pharmacological characteristic is that Melanotan II is non-selective. It is an agonist at MC1R, MC3R, MC4R and MC5R — four of the five melanocortin receptors, which have distinct tissue distributions and distinct functions.

That lack of selectivity is central to its position in the literature. It is why the compound is used as a broad melanocortin probe, and it is also why later research effort went into selective analogues: separating MC1R activity from MC4R activity required different molecules, and the development of receptor-selective melanocortin ligands is a direct consequence.

Research applications reported in the literature include pigmentation biology, melanocortin receptor characterisation and appetite-regulation models via MC4R.

Analytical and handling notes

Two features of the structure have practical consequences:

• Tryptophan at position 6 makes the peptide a primary target for photodegradation. Tryptophan absorbs strongly near 280 nm and both photolyses directly and sensitises singlet-oxygen formation. Amber vials and protection from direct light are proportionate here, not precautionary.
• The lactam bridge is the identity of the molecule. A linear peptide with the same amino acid composition has a mass 18 Da higher — cyclisation is a condensation reaction that loses water. Mass spectrometry distinguishes cyclic from linear unambiguously, which makes mass confirmation on this compound genuinely informative rather than a formality.

Absence of methionine and cysteine removes two common degradation routes, so aside from the tryptophan, it is a robust molecule. Standard handling applies: equilibrate before opening, swirl rather than shake, refrigerate after reconstitution.

Our note on light sensitivity covers the tryptophan issue, and the purity verification guide covers how mass spectrometry confirms structure.

Melanotan II is supplied strictly for laboratory research. We do not provide dosing information and nothing here describes use in humans. Every batch is analysed by an independent laboratory for HPLC purity and mass-spectrometric identity, with batch-matched certificates available on request.

All products and information referenced are for in-vitro research and laboratory use only. Nothing here is medical advice, and no therapeutic claim is made or implied.