Melanotan-I, Melanotan-II and PT-141: Three Compounds, One Dalton Apart

Three melanocortin compounds appear in most catalogues, and two of them differ by a single dalton. That fact decides how a certificate for either one has to be read, and it is the reason this family rewards a careful look at the identity data rather than the label.

Melanotan-I: a linear analog

Melanotan-I, also written MT-1 and carrying the international non-proprietary name afamelanotide, is a thirteen-residue linear peptide: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It is the natural alpha-MSH sequence with two substitutions — norleucine at position 4 in place of methionine, and D-phenylalanine at position 7 in place of the L form.

Both substitutions are stability engineering. Replacing the methionine removes the thioether sulfur and with it the oxidation route that adds 16 daltons to a methionine-containing peptide. Swapping one residue to the D configuration blocks proteases that only recognise L-amino acids. Its formula is C78H111N21O19, mass roughly 1646.8 g/mol, CAS 75921-69-6.

Melanotan-II: the same idea as a ring

Melanotan-II is a different object: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, seven residues with six of them closed into a lactam ring between an aspartate side chain and a lysine side chain. Its formula is C50H69N15O9, mass roughly 1024.2 g/mol, CAS 121062-08-6.

So the two Melanotans are not two sizes of the same thing. One is a thirteen-residue linear chain; the other is a seven-residue macrocycle weighing six hundred daltons less. Cyclising a peptide constrains it into a narrower set of shapes, which is a structural strategy rather than a size reduction. Cyclic and linear peptides covers what closing a ring changes.

The one-dalton problem

Here is the part worth knowing. PT-141 is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. Melanotan-II is the same sequence ending in -NH2 instead of -OH.

A C-terminal amide and a C-terminal free acid differ by the replacement of an NH2 with an OH: roughly one dalton. PT-141 comes in at about 1025.2 and Melanotan-II at about 1024.2, and apart from that terminus they are the same molecule.

That has a practical consequence. A mass spectrum reported to whole-number precision, or a certificate quoting a mass without stating which terminus was expected, does not distinguish these two compounds. Where a laboratory reports the measured mass against a calculated value and the calculated value matches the sequence as written, the identity is settled. Where it reports a rounded figure alone, it is not.

Why cyclisation shows up as eighteen daltons

Closing a lactam ring forms an amide bond between a side-chain carboxyl and a side-chain amine, and forming that bond releases a molecule of water. Water is 18 daltons, so any uncyclised precursor still present in a batch is 18 Da heavier than the finished compound.

On a mass spectrum of Melanotan-II or PT-141, a peak 18 Da above the expected mass is incomplete cyclisation. It is the first thing worth looking for on a certificate for either, and it does not apply to Melanotan-I at all, which has no ring.

The substitution mass spectrometry cannot see

All three compounds contain D-phenylalanine. A D-amino acid and its L counterpart have identical atoms in identical numbers, and therefore identical mass. A mass spectrum cannot tell them apart.

An epimer — the same sequence with that residue in the wrong configuration — is a different compound with the same molecular weight, and it is invisible to the identity test most certificates rely on. What separates them is chromatography: epimers usually resolve on a good reversed-phase gradient because their shapes differ. This is a specific reason to want the chromatogram rather than a summary purity figure. Reading an HPLC chromatogram covers what to look at.

Tryptophan: easy to see, easy to oxidise

All three sequences contain a tryptophan, which is convenient and inconvenient in equal measure. Convenient because tryptophan is the strongest chromophore among the standard residues, so these compounds respond well at 280 nm as well as at 214 nm — unlike a sequence such as Selank, which has no aromatic residues and is nearly invisible at the longer wavelength.

Inconvenient because tryptophan is among the most oxidation-prone residues in the set. Keeping the powder dry, dark and with minimal air exposure is the relevant discipline; how peptides degrade covers the routes.

The three side by side

What to check on a certificate

The calculated mass alongside the measured one, so the terminus is unambiguous. Anything sitting 18 Da high on the two cyclic compounds. The detection wavelength. And net peptide content, which is what tells you how much of the vial is peptide rather than counter-ion and water — see net peptide content and what a third-party peptide test actually measures. Every report we hold is published on the certificates of analysis page.

How they are written

Melanotan-I appears as MT-1, Melanotan 1 and afamelanotide. Melanotan-II appears as MT-2, Melanotan 2 and MT-II. PT-141 appears as PT 141, PT141 and bremelanotide. Within each row these refer to the same compound; across rows they do not.

What we supply

We stock Melanotan-1 10mg, Melanotan-II 10mg and PT-141 10mg, each lyophilised with identity data published on its product page. All are supplied for laboratory research use only. We publish no dosing information, no protocols involving human or veterinary subjects, and no statements about what any of these compounds does in a person, and we do not provide them on request.