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Melanotan I and Melanotan II: structural comparison
Two analogues of the same parent hormone with fundamentally different architectures.
Melanotan I and Melanotan II share a parent hormone and a naming convention, which makes them easy to treat as variants of one compound. They are not: one is linear and one is cyclic, and that difference is more fundamental than the shared name suggests.
This page compares their architectures, their relationships to alpha-melanocyte-stimulating hormone, and the formats stocked.
| Property | Melanotan I | Melanotan II |
|---|---|---|
| Architecture | Linear chain | Cyclic — closed by a lactam bridge |
| Residue count | 13 | 7 |
| Parent hormone | Alpha-melanocyte-stimulating hormone | Alpha-melanocyte-stimulating hormone |
| Relationship to parent | Linear analogue closely tracking the 13-residue sequence | Shortened central region, cyclised |
| Other names | Afamelanotide | MT-II, MTII, bremelanotide precursor |
| Receptor family characterized against | Melanocortin receptors | Melanocortin receptors |
| Related catalogue compound | — | PT-141, a metabolite sharing the cyclic architecture |
| Strengths stocked | 10 mg | 10 mg |
| Storage | Refrigerated, protected from light | Refrigerated, protected from light |
Linear versus cyclic
Melanotan I is a linear 13-amino-acid peptide that closely follows the sequence of alpha-melanocyte-stimulating hormone, the natural 13-residue hormone. It is an analogue in the straightforward sense: the same length, largely the same sequence, with substitutions.
Melanotan II takes a different approach. It reproduces only the central region of the parent hormone, shortened to seven residues, and closes that chain into a ring through a lactam bridge — an amide bond between side chains rather than between the backbone termini.
Cyclisation constrains the peptide conformationally, holding the receptor-engaging residues in a more defined arrangement than a flexible linear chain samples. It also removes the free termini that exopeptidases attack, so cyclic peptides are generally more resistant to enzymatic degradation than linear ones of similar composition.
Shared parent, different constructions
Both are characterized against the melanocortin receptor family, which has several members. Analogues in this group differ in how selectively they engage one member over another, and that selectivity is a structural property arising from which residues occupy which positions.
Both contain a D-amino acid substitution — a residue in the D configuration rather than the L form found in natural sequences. This is a standard peptide engineering technique: most peptidases are specific to L-residues, so a D substitution resists proteolysis and alters local backbone geometry.
The naming convention obscures how different they are. Melanotan I and Melanotan II are not first and second versions of one molecule; they are two distinct constructions from the same starting sequence.
Related compounds and formats
PT-141, catalogued as bremelanotide, is a metabolite of Melanotan II and shares its cyclic heptapeptide architecture, differing at the terminus. It is stocked separately in the HEEZ catalogue. There is no equivalent catalogue relative for Melanotan I.
Both compounds are stocked in a single 10 mg lyophilized format, so the format decision that arises with two-size products applies to neither.
Both contain aromatic residues and are therefore more susceptible to photo-oxidation than peptides without them. Storage in the dark is a specific requirement for both rather than general caution.
Handling and reconstitution
Handling is the same for both. Each is supplied lyophilized and is ambient-stable through transit, so neither requires a cold chain or insulated packaging in shipping. Both go to refrigeration on arrival and are kept out of light.
Because both are stocked at 10 mg, the reconstitution arithmetic is identical: 1 ml of diluent gives 10 mg per ml, 2 ml gives 5 mg per ml, 5 ml gives 2 mg per ml. Bacteriostatic water is the usual choice where a vial will be entered more than once.
The molar difference between them is worth noting even though the mass is the same. Melanotan II is seven residues where Melanotan I is thirteen, so it is the lighter molecule and 10 mg of it represents more molar units. Protocols specified in molar rather than mass terms need each compound's molecular weight from its certificate.
peptcalc.com converts vial mass and target concentration into a diluent volume, and handles molar concentrations where the molecular weight is supplied.
What their certificates show
Both certificates confirm identity by mass spectrometry against the theoretical mass of the intended sequence, and report purity as an HPLC main-peak percentage with the chromatogram attached.
Melanotan II's certificate carries one check the linear compound's does not. Forming its lactam bridge eliminates a water molecule, so the cyclic form is eighteen mass units lighter than its linear precursor. A mass matching the precursor rather than the cyclic product would indicate incomplete cyclisation, which is the characteristic failure mode for a cyclic peptide.
For the same reason, uncyclised precursor and dimeric material — where the bridge joined two molecules instead of closing one — are the impurities worth looking for on a Melanotan II chromatogram. Melanotan I, being linear, shows the ordinary deletion-sequence profile of a synthetic peptide of its length.