Melanotan I vs Melanotan II: Structural Differences Explained

Key takeaways

• Melanotan I (MT-1, NDP-alpha-MSH / afamelanotide, CAS 75921-69-6) is a 13-residue linear analog of alpha-MSH with the formula C78H111N21O19 and a molecular weight near 1646.85 g/mol.
• Melanotan II (MT-2, CAS 121062-08-6) is a 7-residue cyclic lactam analog with the formula C50H69N15O9 and a molecular weight near 1024.2 g/mol.
• The defining structural distinction is topology: MT-1 is a linear peptide chain, while MT-2 is cyclized through a side-chain lactam bridge between an aspartate carboxyl and a lysine amine.
• Both share the conserved melanocortin His-D-Phe-Arg-Trp core and the Nle4 / D-Phe7 substitutions that distinguish these analogs from native alpha-MSH.
• These are lyophilized research peptides handled under cold-chain storage; identity (LC-MS) and purity (HPLC) belong on a per-batch certificate of analysis.

Melanotan I and Melanotan II are frequently grouped together because their names suggest two versions of the same molecule. Structurally, they are quite different peptides within the melanocortin analog family, differing in length, topology, and molecular weight. This guide compares them strictly as chemical structures: amino acid sequence, residue count, cyclization, and molecular formula. It makes no claims about biological activity, use, or outcomes of any kind.

If you handle either compound as a research material, the structural facts below are the ones that show up on a certificate of analysis (COA) and govern reconstitution and storage decisions. For broader context on the receptor family these analogs derive from, see our melanocortin research peptide class overview.

Both Are Melanocortin Analogs, Not the Same Molecule

Melanotan I and Melanotan II are synthetic analogs of alpha-melanocyte-stimulating hormone (alpha-MSH), a member of the melanocortin peptide family. Native alpha-MSH is a 13-residue linear peptide. Both analogs were developed from alpha-MSH research at the University of Arizona in the 1980s, and both retain the conserved melanocortin pharmacophore region, the His-Phe-Arg-Trp motif, that is shared across this peptide class.

The shared origin is why the names look like a numbered pair. But Melanotan I keeps the full-length linear architecture of alpha-MSH, while Melanotan II is a deliberately shortened, cyclized fragment. Treating them as interchangeable is a structural error: they have different sequences, different residue counts, different topologies, and molecular weights that differ by more than 600 g/mol. PT-141 (bremelanotide), described in our PT-141 structure guide, is a further structural relative derived from the Melanotan II scaffold, which underscores how this family branches from a common core.

Melanotan I: A 13-Residue Linear Analog

Melanotan I is also written as [Nle4, D-Phe7]-alpha-MSH and abbreviated NDP-alpha-MSH (or NDP-MSH). Its international nonproprietary name is afamelanotide, and it carries CAS number 75921-69-6.

Structurally, MT-1 preserves the full 13-amino-acid linear backbone of alpha-MSH with two substitutions: norleucine (Nle) replacing methionine at position 4, and D-phenylalanine (D-Phe) replacing L-phenylalanine at position 7. The D-amino acid substitution and the norleucine swap are the modifications that distinguish this analog from the native sequence. The chain is N-acetylated at the amino terminus and amidated at the carboxy terminus.

• Sequence: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2
• Residue count: 13 amino acids
• Topology: linear (no intramolecular ring)
• Molecular formula: C78H111N21O19
• Molecular weight: approximately 1646.85 g/mol
• CAS: 75921-69-6; also known as NDP-alpha-MSH, afamelanotide

Melanotan II: A 7-Residue Cyclic Lactam

Melanotan II (MT-2) is a markedly smaller and structurally distinct peptide, carrying CAS number 121062-08-6. Rather than preserving the full alpha-MSH chain, it condenses the active region into a cyclized seven-residue structure.

Its sequence is commonly written Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2. The cyclization is a side-chain lactam bridge: during synthesis, the gamma-carboxyl group of the aspartate residue and the epsilon-amino group of the lysine residue have their orthogonal protecting groups removed and are joined through carbodiimide-mediated lactamization, forming a ring. An N-acetyl-norleucine cap completes the molecule. Like MT-1, it carries the D-phenylalanine substitution and the His-D-Phe-Arg-Trp melanocortin core, but here that core is constrained inside a ring rather than presented on an open chain.

• Sequence: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2
• Residue count: 7 amino acids
• Topology: cyclic lactam (Asp side-chain carboxyl to Lys side-chain amine bridge)
• Molecular formula: C50H69N15O9
• Molecular weight: approximately 1024.2 g/mol
• CAS: 121062-08-6

Side-by-Side Structural Comparison

The table below summarizes the structural attributes only. It does not address activity, use, or outcomes. The Ascend Bio Labs column reflects how we document these compounds: each batch ships with a publicly retrievable certificate of analysis tied to a unique batch ID printed on the vial.

Why the Topology Difference Matters for Identity Confirmation

The most consequential difference between these two peptides for laboratory handling is topology. MT-1 is linear; MT-2 is cyclic. Cyclization changes the exact monoisotopic and average mass and produces a different fragmentation pattern under mass spectrometry, which is precisely how an analytical lab distinguishes a correctly cyclized lactam from a linear or incompletely cyclized impurity.

Because the two compounds differ by more than 600 g/mol and by seven residues, their mass spectra are unambiguous when run side by side. This is why identity confirmation by LC-MS, paired with purity quantification by HPLC, is the standard analytical pairing for melanocortin research peptides. A certificate of analysis that reports both the expected molecular weight and an HPLC purity figure lets a researcher confirm they are working with the intended structure rather than a mislabeled or off-spec material.

Handling, Reconstitution, and Storage (Structure-Driven)

Both Melanotan I and Melanotan II are supplied as lyophilized (freeze-dried) powders. Reconstitution for research handling is typically performed with bacteriostatic or sterile water added gently down the vial wall, swirled rather than shaken to avoid mechanical stress on the peptide. Once reconstituted, peptide solutions are generally kept refrigerated and protected from light; lyophilized powder is stored frozen for longer-term holding. For a fuller reference on cold-chain handling that applies across peptide classes, see our peptide storage and cold-chain handling guide.

Storage parameters are properties of the material and the batch, not of any application. The structural features above, an amidated terminus, an acetyl cap, and in MT-2 a constrained lactam ring, are the kinds of details that belong on the documentation accompanying a research-grade vial. For an example of how a short, fully linear peptide is documented by sequence and mass in this same format, compare our Epithalon tetrapeptide reference.

How Ascend Bio Labs Documents These Compounds

Ascend Bio Labs synthesizes, tests, stores, and ships entirely within the United States, with no overseas transshipment. Every batch is tested by independent third-party laboratories using HPLC for purity and LC-MS for molecular identity, and the resulting certificate of analysis is published publicly. Each vial carries a unique batch ID that links directly to that batch's COA, so the molecular weight and purity you read here can be matched against the document for the exact lot in hand.

These materials are sold strictly for research use only. We describe what each molecule is, its sequence, residue count, topology, formula, and molecular weight, and deliberately make no statements about biological effects, use in humans or animals, or outcomes of any kind.

Related research notes

• What Is PT-141 (Bremelanotide)? Melanocortin Peptide Structure
• Melanocortin Research Peptides: Class Overview and Members
• What Is Epithalon? Tetrapeptide Sequence and Molecular Weight
• Peptide Storage and Cold-Chain Handling: A Research Reference