Melanotan II

A synthetic cyclic heptapeptide (cyclic lactam, 7 residues) studied as a conformationally constrained reference ligand in class A GPCR binding, structure-activity chemistry, and structural-biology research.

Molecular Profile

Type
Synthetic cyclic heptapeptide (cyclic lactam)
Molecular formula
C50H69N15O9
Molecular weight
1,024.18 g/mol
CAS number
121062-08-6
Amino acids
7
Sequence
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2
Modification
N-terminal acetylation; C-terminal amide; cyclic lactam bridge between the Asp side-chain γ-carboxyl and the Lys side-chain ε-amino group; contains norleucine (Nle) in place of methionine and D-phenylalanine in place of L-phenylalanine.

Mechanism & Target Class

Melanotan II is a conformationally constrained cyclic lactam heptapeptide. It retains the conserved His-Phe-Arg-Trp core motif, with three engineered modifications relative to the parent linear sequence: substitution of methionine by norleucine, inversion of L-phenylalanine to D-phenylalanine, and a side-chain-to-side-chain lactam bridge (Asp–Lys) that locks the backbone into a defined turn conformation. These changes are associated with reduced susceptibility to enzymatic cleavage in vitro and constrain the bioactive conformation. The constrained scaffold is widely used as a reference ligand for characterizing the binding and selectivity profile of class A (rhodopsin-like) G-protein-coupled receptors in radioligand and structural-biology studies.

Storage & Handling

Lyophilized
-20°C or colder for long-term storage; protected from light and moisture in a desiccated environment.
Handling
Avoid repeated freeze-thaw cycles; aliquot before freezing. Water-soluble; handle as a research-use-only laboratory reagent following standard peptide-handling practice.

Primary Database

PubChem CID 92432 ↗

References (22)

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