Melanotan I (Afamelanotide)

1 Identity

Melanocortin receptor ligands. Synthetic linear 13-residue alpha-MSH analog carrying four structural modifications, one of them a non-proteinogenic residue and one of them a D-residue. It is the active moiety of an FDA-approved drug product. Free-peptide CAS 75921-69-6 and acetate-salt CAS 1566590-77-9 are both commonly published.

Sequence

Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2; thirteen residues. Four modifications, every one of them load-bearing: N-terminal acetyl on Ser1; C-terminal carboxamide on Val13; NORLEUCINE substituted for methionine at position 4, which is a non-proteinogenic residue and which removes the only sulfur atom the parent hormone has; and D-phenylalanine at position 7, which is what makes the chiral method mandatory rather than optional. No cysteine, no disulfide, no acyl chain, no PEG. Two protonatable side chains (His6, Arg8) plus the Lys11 epsilon-amine, so acetate stoichiometry can run to three equivalents. Written as a bare thirteen-letter string with no acetyl, no amide, no Nle and no D-Phe, this sequence describes a different compound.

Molecular formula

C78H111N21O19 (free peptide, salt-free). Acetate salt written by suppliers as C78H111N21O19 . XC2H4O2 with the stoichiometry literally undeclared. Alpha-MSH C77H109N21O19S. Des-acetyl form C76H109N21O18. Des-amido (free acid) form C78H110N20O20. Trp9-oxidized form C78H111N21O20.

Average mass

1,646.87 Da (C78H111N21O19), from the formula on IUPAC 2021 abridged conventional atomic weights: 1,646.874. Comparators: alpha-MSH 1,664.91 (+18.03); des-acetyl 1,604.84 (-42.04); des-amido free acid 1,647.86 (+0.98); Trp9-oxidized 1,662.87 (+16.00); Melanotan II 1,024.20. Acetate burden: three equivalents is +180.16 Da, an 11 percent w/w burden on the vial, and the supplier's own "XC2H4O2" is an honest admission that the stoichiometry is not fixed in this trade.

Monoisotopic mass

1,645.83651 Da neutral (C78H111N21O19). [M+H]+ 1,646.84379; [M+2H]2+ 823.92553; [M+3H]3+ 549.61945. Comparators: alpha-MSH 1,663.79293 (+17.96, and it imports a sulfur atom this article does not contain); des-acetyl 1,603.82595 (-42.01); des-amido free acid 1,646.82053 (+0.98); Trp9-oxidized 1,661.83143 (+16.00). The arithmetic trap on this record: the des-amido degradant's monoisotopic mass, 1,646.82, sits 0.05 Da from the parent's average mass, 1,646.87. A certificate reading "1646.8" with no basis declared is simultaneously consistent with the product and with its principal hydrolytic degradant.

Salt / variant note

Salt basis is A genuine two-molecule commercial split under one name. (1) Free peptide, C78H111N21O19, 1,646.87 average / 1,645.83651 monoisotopic, CAS 75921-69-6. (2) Acetate salt, written by one seller as C78H111N21O19 . XC2H4O2, CAS 1566590-77-9 — the stoichiometry is literally "X", undeclared, and with His6, Arg8 and Lys11 basic it can run to three equivalents, up to +180.16 Da and an 11 percent w/w burden. Chemically distinct substitution risks, each with its own arithmetic: (3) alpha-MSH itself, Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, C77H109N21O19S, 1,664.91 / 1,663.79293 — methionine for norleucine is +18.03 Da on average mass and imports a sulfur atom the product does not contain, so an elemental or isotope-pattern result showing sulfur is dispositive. (4) Des-acetyl afamelanotide, C76H109N21O18, 1,604.84 / 1,603.82595, exactly -42.01 Da monoisotopic. (5) des-amido (free acid) afamelanotide, C78H110N20O20, 1,647.86 / 1,646.82053 — the principal hydrolytic degradant and the trap described in the mass fields above: its monoisotopic value sits 0.05 Da from the parent's average value. (6) Trp9-oxidized species, C78H111N21O20, 1,662.87 / 1,661.83143, +16.00 Da. (7) Melanotan II, C50H69N15O9, 1,024.20 — it shares the trade-name stem and nothing else, and it is a cyclic heptapeptide rather than a linear 13-mer. (8) the isobaric class no mass measurement reaches: norleucine is exactly isobaric with leucine and isoleucine, so an all-Leu4 impostor weighs the same to every decimal place; and D-Phe7 is exactly isobaric with L-Phe7, so the all-L impostor — which is a different compound with different pharmacology — is invisible to every achiral method on the certificate. Those two isobaric classes are the whole reason the chiral method and a documented amino acid analysis resolution are mandatory here rather than confirmatory.

2 Class & testing panel

Form

Single article

Testing panel

P3 — panel definition

3 Primary sources & evidence

The index reports the design and provenance of the literature, not a conclusion about effect.

Published literature exists and is the strongest in its class — and it attaches to a product this company will not sell, in a dosage form the research market does not trade. Human randomized placebo-controlled trials of the controlled-release afamelanotide implant: Langendonk et al., New England Journal of Medicine 2015;373:48-59, registered as NCT01605136 and NCT00979745; these supported EMA authorization in 2014 and FDA approval in October 2019 under NDA 210797. Behind that sits roughly four decades of in-vitro melanocortin receptor pharmacology dating to Sawyer et al., Proceedings of the National Academy of Sciences USA 1980;77:5754 — the publication that also placed the [Nle4, D-Phe7] structure in the public domain — and a moderate rodent literature. What does not exist is any controlled human study of bulk lyophilized peptide in the presentation the research market trades: the human dataset belongs to one specific implant dosage form used under specialist supervision in a rare disease, and it does not read across to the article.

4 Storage & specification

Storage

Not offered, so no condition is qualified and no lot is held. The condition that would apply: lyophilized solid, -20 degrees C plus or minus 5 degrees C, desiccated over silica, protected from light because of Trp9 and Tyr2, sealed under argon or nitrogen headspace, vials equilibrated to ambient temperature before opening. Moisture control would be treated as critical rather than routine, because the C-terminal amide hydrolyzes to the free acid and that degradant is the one the certificate cannot distinguish from the parent without high resolution.

Shelf life

Not established — no lot will be purchased, imported or held. Had the article been offered, the provisional retest interval would be 24 months at -20 degrees C plus or minus 5 degrees C, desiccated, stated as provisional pending the company's own ICH Q1A(R2)-style stability data, with des-amido, des-acetyl and Trp9-oxidized species reported individually at every pull rather than pooled.