Melanotan-I, Melanotan-II and PT-141 Compared: Structure, Mass and Identity Data

A core facility receives two sample vials for identity confirmation, one labeled Melanotan-II and one labeled PT-141. The technician runs both and the software reports masses of 1024 and 1025. Job done? Not quite. Those two compounds are the same cyclic sequence with a different group at one end, and a one-dalton gap reported as whole numbers is exactly the kind of result that can hide a mix-up. Add Melanotan-I, which shares a name with Melanotan-II but is a very different molecule, and this family becomes a useful case study in reading structures and identity data carefully.

Three structures at a glance

Melanotan-IMelanotan-IIPT-141
Other namesMT-1, MT-IMT-2, MT-IIPT141
Residues1377
TopologyLinearCyclic lactamCyclic lactam
C-terminusAmideAmideFree acid
FormulaC78H111N21O19C50H69N15O9C50H68N14O10
Average mass (g/mol)about 1646.8about 1024.2about 1025.2
CAS number75921-69-6121062-08-6189691-06-3

Names within a column are the same compound. Names across columns are not, even when they look alike. Individual profiles are available for Melanotan-I, Melanotan-II and PT-141.

Melanotan-I: a modified linear chain

Melanotan-I has the sequence Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It follows the thirteen-residue alpha-MSH sequence with two deliberate substitutions. Position 4 carries norleucine instead of methionine, and position 7 carries D-phenylalanine instead of the natural L form.

Both changes are chemical stabilization strategies. Norleucine has the same side-chain length as methionine but no sulfur atom, which removes the methionine sulfoxide pathway that would otherwise add 16 Da to the molecule on oxidation. Inverting one residue to the D configuration makes the chain a poorer substrate for proteases that recognize only L-amino acids. The N-terminal acetyl group and C-terminal amide cap both ends of the chain.

Melanotan-II and PT-141: one ring, two endings

Melanotan-II is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2. Six of its seven residues form a ring closed by a lactam bond between the side-chain carboxyl of aspartic acid and the side-chain amine of lysine. It is not a shortened Melanotan-I; it is a separate macrocyclic design about 620 Da lighter, whose ring restricts the conformations the molecule can adopt. Cyclization is a structural strategy, not a reduction in size.

PT-141 is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. Compare that with Melanotan-II and the only difference is the final group: a free carboxylic acid instead of an amide. Replacing NH2 with OH adds 0.984 Da, and that single change separates the two compounds. The formulas reflect it: PT-141 has one fewer nitrogen, one fewer hydrogen and one more oxygen.

What that means for identity data

Return to the core facility. A report stating “mass 1024” and another stating “mass 1025” would be consistent with the labels, but rounding, calibration error or a report that does not state which form was expected could all blur the answer. Identity is well supported when a report lists a calculated mass derived from the full structure, including the terminus, and a measured mass that agrees with it within the stated accuracy of the instrument. A lone rounded figure is weak evidence in this family specifically.

A second practical step is to analyze both vials in the same sequence on the same instrument. Because the two compounds differ only at the C-terminus, their retention under reverse-phase conditions is similar, but a free acid and an amide do not carry the same charge under every mobile-phase condition, so their elution behavior can differ. A side-by-side run, with each measured mass compared against its own calculated value, gives the facility a direct comparison rather than two isolated numbers. Retention time on its own remains supporting evidence rather than proof of identity.

Some practical checks for anyone reviewing documentation on these compounds:

  1. Does the calculated mass match the correct terminus, amide for Melanotan-II and acid for PT-141?
  2. For the two cyclic compounds, is there any signal about 18 Da above the main mass? Forming the lactam bond releases one water molecule, so any uncyclized linear precursor sits 18 Da high. That check does not apply to Melanotan-I, which has no ring.
  3. Is a chromatogram provided, not just a purity figure?
  4. Is the detection wavelength stated for each of the three peptides?

The D-residue problem mass cannot solve

All three compounds contain D-phenylalanine. A D-amino acid has exactly the same atoms as its L counterpart, so a molecule with the wrong configuration at that position has exactly the same mass as the intended compound. Mass spectrometry cannot distinguish them.

Chromatography often can. The two diastereomers have different shapes and interact differently with a reverse-phase stationary phase, so a good gradient may resolve them as separate peaks. This is one of the clearest reasons to want the actual trace. What to look for in one is described in how to read an HPLC chromatogram.

Tryptophan: a strong signal and a weak point

Each of the three sequences includes one tryptophan. Tryptophan is the strongest ultraviolet absorber among the standard amino acids, so these compounds give a useful response at 280 nm as well as at 214 nm, where the peptide bond absorbs. That makes detection straightforward and allows a second wavelength to be used as a check.

The same residue is one of the more easily oxidized. Oxidation products of tryptophan appear at higher masses than the parent, commonly in steps of 16 Da, and as new peaks in the chromatogram. Anyone comparing data collected at different times should keep that possibility in mind.

Where Battle Born fits

Battle Born supplies these compounds as lyophilized laboratory reference materials to research purchasers in the USA, and each product has an independent reverse-phase HPLC result published for it. The catalog is on the shop page. Structural and analytical information is provided for research reference only.

Questions

Are Melanotan-I and Melanotan-II the same peptide in different sizes?

No. Melanotan-I is a 13-residue linear peptide; Melanotan-II is a 7-residue cyclic lactam. They share some residues but are distinct designs.

How can PT-141 be told apart from Melanotan-II?

By the C-terminus. PT-141 ends in a free acid and Melanotan-II in an amide, a mass difference of about 0.98 Da that requires an accurately reported measured mass against a calculated value.

What does a signal 18 Da high indicate?

For the two cyclic compounds, it suggests linear precursor that did not complete ring closure, since cyclization releases one molecule of water.


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