Melanotan I is a synthetic 13-residue analog of α-melanocyte-stimulating hormone (α-MSH). It is widely identified in research literature as [Nle4,D-Phe7]-α-MSH, NDP-α-MSH, or NDP-MSH.

The peptide preserves the overall sequence framework of native α-MSH while introducing two important residue changes: methionine at position 4 is replaced by norleucine (Nle), and L-phenylalanine at position 7 is replaced by D-phenylalanine (D-Phe).

These substitutions produce a useful research ligand for investigating melanocortin receptor recognition, MC1R-associated signaling, melanogenesis, receptor internalization, and structure–activity relationships within the α-MSH family.

Product Information

A Modified α-MSH Research Ligand

Native α-MSH contains the sequence motif His-Phe-Arg-Trp, which plays an important role in melanocortin receptor recognition.

Melanotan I retains this pharmacophore while incorporating D-Phe at position 7. The stereochemical change at this residue is particularly important: it alters the conformational and receptor-binding properties of the peptide and is one reason NDP-α-MSH is frequently used instead of native α-MSH in melanocortin receptor experiments.

The Nle4 substitution also removes the sulfur-containing methionine side chain present in endogenous α-MSH.

For scientists comparing α-MSH analogs, these modifications should be considered part of the molecular identity rather than optional sequence variations.

MC1R and Melanogenesis Research

MC1R is a G protein-coupled melanocortin receptor expressed prominently in melanocytes. Activation of this pathway is associated with cAMP signaling and regulation of melanogenic processes.

NDP-α-MSH has therefore been used in studies involving melanocyte receptor binding, intracellular signaling, tyrosinase-associated responses, receptor internalization, and melanin synthesis.

Its relevance is not limited to MC1R. NDP-α-MSH is a potent melanocortin agonist with activity at several melanocortin receptor subtypes, so receptor-selectivity assumptions should be avoided when experiments extend beyond melanocyte systems.

Why Sequence Definition Matters

For purchasing and experimental reproducibility, the complete modified structure should be specified:

Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2

Writing only “α-MSH analog” is insufficient because multiple α-MSH-derived sequences with substantially different receptor pharmacology are available.

The N-terminal acetyl group, C-terminal amide, Nle4 substitution, and D-Phe7 stereochemistry should all be included when comparing materials across suppliers or publications.

Research Applications

Melanotan I can support melanocortin receptor binding studies, MC1R signaling experiments, melanocyte biology, cAMP pathway research, melanogenesis models, receptor internalization studies, and structure–activity comparisons of α-MSH analogs.

It is also a useful parent sequence for evaluating residue substitutions, truncations, labeling strategies, or other modified melanocortin ligands.

Researchers requiring related sequences can use Custom Peptide Synthesis.

Experimental and Procurement Considerations

For receptor and cell-based experiments, peptide identity alone does not define experimental performance. Concentration, purity, counterion, reconstitution conditions, storage history, and assay model can influence observed activity.

We recommend confirming both D-Phe stereochemistry and terminal modifications when sourcing NDP-α-MSH, particularly when comparing material across batches or vendors.

Analytical HPLC and mass spectrometry can support chromatographic purity and molecular identity. Additional information is available through Peptide Quality Control.

Frequently Asked Questions

What is the difference between Melanotan I and native α-MSH?

Melanotan I contains Nle at position 4 and D-Phe at position 7, whereas native α-MSH contains Met4 and L-Phe7. The remaining sequence framework and terminal acetylation/amidation are closely related to α-MSH.

Is Melanotan I the same as NDP-α-MSH?

Yes. In research literature, Melanotan I, NDP-α-MSH, NDP-MSH, and [Nle4,D-Phe7]-α-MSH are commonly used for the same 13-residue modified α-MSH sequence.

Is Melanotan I an MC1R-selective peptide?

It is highly relevant to MC1R research but should not be described as strictly MC1R-selective. NDP-α-MSH can activate several melanocortin receptor subtypes.

What is the difference between Melanotan I and Melanotan II?

Melanotan I is a linear 13-residue α-MSH analog, whereas Melanotan II is a much shorter cyclic heptapeptide derived from the melanocortin pharmacophore. They should not be treated as interchangeable research reagents.

Research Use Only.