Melanotan II, commonly abbreviated MT-II, is a synthetic cyclic melanocortin peptide derived from the biologically important receptor-binding region of α-MSH.

Unlike the 13-residue linear NDP-α-MSH sequence, MT-II condenses key melanocortin pharmacophore elements into a cyclic heptapeptide containing norleucine and D-phenylalanine.

Its constrained structure makes MT-II a widely used research ligand for investigating melanocortin receptor pharmacology, receptor–ligand recognition, peptide cyclization, signaling pathways, and melanogenesis-related biology.

Product Information

A Conformationally Constrained Melanocortin Analog

A defining feature of MT-II is its side-chain lactam cyclization.

The Asp and Lys residues form the cyclic scaffold around the central melanocortin recognition sequence containing His-D-Phe-Arg-Trp. This conformational constraint distinguishes MT-II from linear α-MSH analogs and makes it useful for studying how peptide topology affects receptor affinity, signaling, and subtype pharmacology.

For researchers working on cyclic peptide design, MT-II is also a useful reference scaffold for investigating relationships between ring geometry and melanocortin receptor activity.

Melanocortin Receptor Pharmacology

MT-II is a potent but relatively nonselective melanocortin receptor agonist.

It has been used experimentally with MC1R, MC3R, MC4R, and MC5R systems. In melanocyte-focused studies, MC1R is especially relevant because of its role in pigmentation signaling. In other experimental systems, activity at MC3R and MC4R may become equally important.

This broader receptor profile is an important distinction for experimental design.

We do not recommend describing MT-II simply as an “MC1R-specific peptide.” Such wording can obscure the broader pharmacology of the molecule and complicate interpretation in systems expressing multiple melanocortin receptor subtypes.

Why Cyclization Must Be Specified

For MT-II, the sequence alone is not sufficient to define the intended research material.

A linear peptide containing the same residues would not be chemically equivalent to the cyclic molecule. Procurement specifications should therefore include:

Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH2

and explicitly identify the Asp–Lys lactam linkage.

The presence of D-Phe and the two terminal modifications should also be verified.

This structural precision is particularly important when ordering custom analogs or comparing MT-II derivatives in structure–activity studies.

Research Applications

MT-II can be used in melanocortin receptor binding and activation studies, melanocyte signaling research, cAMP assays, melanogenesis models, receptor subtype comparisons, cyclic peptide structure–activity studies, and ligand optimization programs.

It can also provide a parent scaffold for preparing analogs with altered ring size, stereochemistry, side-chain substitutions, receptor selectivity, or labeling.

Alan Scientific can evaluate related cyclic or modified sequences through Custom Peptide Synthesis.

Experimental and Procurement Considerations

For scientists and lab managers, three specifications are particularly important for MT-II: cyclization topology, stereochemistry, and salt form.

The free peptide has a theoretical molecular weight of approximately 1024.2 Da. Reported mass values can differ when a commercial material is represented as an acetate or other salt, so molecular weight comparisons should always consider the form specified on the COA.

For receptor pharmacology experiments, we also recommend maintaining consistent peptide concentration, solvent conditions, counterion, and storage history across comparator compounds.

HPLC and mass spectrometry can support purity and identity assessment. Details of available analytical characterization are provided under Peptide Quality Control.

Frequently Asked Questions

What is the sequence of Melanotan II?

The commonly used structural notation is:

Ac-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-NH2

The peptide contains seven amino-acid residues and an Asp–Lys side-chain lactam ring.

Is Melanotan II a linear or cyclic peptide?

MT-II is a cyclic peptide. The ring structure is an essential part of its molecular identity and distinguishes it from linear melanocortin analogs such as NDP-α-MSH.

Which melanocortin receptors does MT-II activate?

MT-II is generally used as a relatively nonselective melanocortin agonist with activity at MC1R, MC3R, MC4R, and MC5R. The receptor subtype most relevant to an experiment depends on the biological model being studied.

What is the main structural difference between Melanotan I and Melanotan II?

Melanotan I is a linear 13-residue α-MSH analog. Melanotan II is a shorter cyclic heptapeptide that retains a compact melanocortin recognition motif within a conformationally constrained lactam ring.

Research Use Only.