Melanotan II

Melanotan II is a synthetic cyclic heptapeptide analogue of α-melanocyte-stimulating hormone. It shares its macrocyclic core with PT-141 and differs from it at a single atom position — a distinction covered in detail below, because it is the one specification error most likely to appear on a melanocortin peptide listing.

Identity and classification

Melanotan II is catalogued as a non-selective melanocortin agonist, in contrast to PT-141, which is described principally as MC4R-directed. That difference in receptor selectivity profile is the pharmacological classification associated with the two molecules and is stated here as classification only.

The name is also written MT-II or MT2. It should not be confused with “melanotan I”, which is afamelanotide — a linear 13-residue peptide, not a cyclic heptapeptide, and a structurally distinct molecule despite the shared naming.

Structure

Written in full: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂.

• Lactam macrocycle. A side-chain-to-side-chain amide bond between the Asp2 carboxyl and the Lys7 amine closes the ring, constraining the His-D-Phe-Arg-Trp pharmacophore.
• Norleucine replaces the methionine of the native hormone — isosteric, but with no sulfur and therefore no oxidation liability.
• D-phenylalanine at position 7 of the parent numbering, inverting the stereocentre.
• C-terminal carboxamide. The chain terminates in –NH₂. This is the sole difference from PT-141.

The one-dalton problem

Melanotan II and PT-141 differ only in whether the C-terminus is an amide or a free acid: 1024.18 against 1025.2, a difference of roughly 1 Da on molecules of a thousand daltons.

Practical consequences worth internalising:

• Low-resolution MS cannot reliably tell them apart. A nominal-mass instrument reporting “1024” or “1025” has not distinguished the two compounds, and neither has a certificate that quotes only a nominal mass.
• They are chromatographically separable. The amide is slightly less polar and elutes marginally later on reverse phase. A co-injection resolves them where a mass measurement may not.
• Incomplete C-terminal amidation is itself the relevant synthesis impurity. For melanotan II, residual free-acid material is PT-141 — the impurity is the other product, which is an unusual and easily overlooked situation.

A supplier quoting the same molecular weight for both compounds has made an error, and it is the specific error to look for on melanocortin listings.

Specification and characterisation

• RP-HPLC purity at 214 nm, with 280 nm secondary detection via the tryptophan.
• High-resolution mass confirmation against 1024.18 — resolution is not optional for this compound, for the reason above.
• Ring closure. The uncyclised linear precursor differs by +18 Da, the water lost on lactam formation.
• Tryptophan photodegradation. Trp is the most light-sensitive standard residue; oxidation products include N-formylkynurenine.
• Counter-ion and net peptide content. Commonly supplied as the acetate.

Handling and stability

Store sealed at 2–8 °C, dry, in the dark. As with PT-141, light protection is the specific requirement, driven by the tryptophan rather than by generic caution. No cysteine and no methionine — the norleucine substitution removed the sulfur — so the compound is comparatively robust as a dry solid, and the constrained macrocycle is conformationally stable.

Equilibrate in a desiccator before opening.

Related compounds in this library

PT-141, the free-acid counterpart, as discussed throughout. KPV is also derived from α-MSH but from the C-terminal end of the hormone and as a linear tripeptide; it shares the parent but not the structure.

References

Chemical, specification and analytical sources. This list is deliberately limited to chemistry and analytical references.

• Cayman Chemical, melanotan II record — formula, molecular weight, structure
• Chemsrc, CAS 121062-08-6 — registry and mass data
• ChemicalBook, melanotan II property record — independent formula confirmation
• Bachem, Handling and Storage Guidelines for Peptides — tryptophan photolability, cyclic peptide handling

Cosmic Aminos supplies this material as a laboratory reagent for in-vitro research use only. It is not a drug, food, cosmetic or dietary supplement, is not approved by the Food and Drug Administration for any use, and is not for human or veterinary consumption. No dosing, administration or preparation guidance is provided.