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Molecular Weight
Purity
Storage
Appearance
Solubility
01
Melanotan II (MT-II) is a synthetic cyclic peptide built around the His-Phe-Arg-Trp core shared by all melanocortin peptides. Its sequence is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH₂: a ring closed by an amide (lactam) bond between the side chains of aspartate and lysine, with an acetylated norleucine outside the ring.
Compared with the linear, full-length Melanotan I, it is much shorter and conformationally constrained, and it activates several melanocortin receptors with high potency but little selectivity. It is closely related to PT-141 (bremelanotide), which differs only at the C-terminus. It is supplied as a lyophilized reference compound for in vitro research on melanocortin receptors and cyclic peptides only.
02
Melanotan II’s structure is defined by its lactam ring.
Lactam bridge
The side-chain carboxyl of Asp2 is joined to the side-chain amine of Lys7, forming a 23-membered ring. Unlike a disulfide, this amide bond is not affected by reducing agents and is chemically robust under normal conditions.
Core motif
His-D-Phe-Arg-Trp sits inside the ring. The D-configured phenylalanine, as in Melanotan I, increases potency and resistance to enzymes.
Exocyclic Nle1
An acetylated norleucine sits outside the ring, adding hydrophobicity; there is no methionine to oxidise.
C-terminal amide
The ring’s C-terminus is amidated. Replacing this amide with a free acid gives PT-141.
Charge
With the Asp and Lys side chains used in the ring and both termini capped, the main charges are Arg5 (positive) and partly His3, giving a net charge of about +1 to +2.
03
In vitro research treats Melanotan II as a potent, non-selective melanocortin agonist.
Receptor profile
Binding and cAMP assays in cells expressing individual receptors show activity at MC1R, MC3R, MC4R and MC5R, with limited selectivity between them.
Effect of cyclisation
Constraining the backbone in a ring is thought to pre-organise the peptide in receptor-compatible shapes, which is associated with higher potency at several receptors, including MC4R, compared with linear analogues.
Structure–activity comparisons
Comparisons with linear Melanotan I and with PT-141 help separate the contributions of ring formation and C-terminal chemistry to receptor preference.
These findings are cited as research context only; no effects are claimed for this material.
04
Melanocortin receptor panels
A non-selective reference agonist and potency benchmark in binding and cAMP assays.
Cyclic peptide analytics
A model lactam-bridged peptide for developing methods that separate cyclic peptides from ring-opened products and confirm ring integrity by MS/MS.
Structural studies
A reference for NMR and circular dichroism studies of constrained peptides.
PT-141 comparisons
The essential control when assays must distinguish the C-terminal amide (MT-II) from the free acid (PT-141).
05
Storage
Store the lyophilized powder at −20 °C, sealed, desiccated and protected from light.
Light sensitivity
Trp6 can photo-oxidise to kynurenine-type products. Handle under subdued light and use amber containers.
Amide hydrolysis
Under acidic or basic stress, the C-terminal amide can hydrolyse to the free acid, converting MT-II into PT-141. Keep solutions near neutral to mildly acidic pH and cold.
Lactam stability
The ring bond is stable under normal conditions and is opened only by prolonged exposure to strong acid or base.
Reconstitution
Soluble in water and DMSO. Aliquot into single-use volumes in low-binding tubes and freeze.
06
The key analytical tasks are confirming ring integrity and separating MT-II from PT-141.
HPLC
Reversed-phase C18 with a TFA gradient typically gives a sharp peak. Detect at 214 nm or 280 nm (Trp). An optimised gradient separates MT-II from PT-141, whose free acid changes its retention.
Mass spectrometry
ESI gives [M+H]⁺ at m/z 1024.5 and [M+2H]²⁺ at m/z 512.8 (monoisotopic). MS/MS of the cyclic peptide gives ring-opening fragments that confirm the lactam.
MT-II versus PT-141
The two differ by about 0.98 Da. Pure samples are easy to identify, but in mixtures the natural ¹³C isotope peak of MT-II lies within about 0.02 Da of PT-141’s main peak, so high-resolution MS or chromatographic separation is needed to quantify one in the presence of the other.
Impurity profile
Typical checks include PT-141 (from amide hydrolysis), Trp oxidation products, ring-opened forms (+18 Da), the L-Phe epimer and incompletely cyclised synthesis intermediates.
07
A lactam bridge: an amide bond between the side-chain carboxyl of aspartate and the side-chain amine of lysine, forming a 23-membered ring. Unlike a disulfide, it is not affected by reducing agents.
Restricting the backbone holds the His-D-Phe-Arg-Trp core in receptor-compatible shapes, which is associated with high potency at several melanocortin receptors. Selectivity between receptor subtypes remains limited.
They are identical except at the C-terminus (amide versus acid), a difference of about 0.98 Da. In mixtures, MT-II’s natural isotope peak overlaps PT-141’s main peak, so high-resolution MS or HPLC separation is needed.
Tryptophan oxidation products, PT-141 formed by hydrolysis of the C-terminal amide, and under harsh conditions ring-opened forms (+18 Da).
Acid and base stress (to generate amide hydrolysis to PT-141 and any ring opening), peroxide (for Trp and His oxidation), light exposure following standard photostability practice (for Trp), and elevated temperature. A suitable method must separate all of these products from the main peak.
No. It is supplied strictly as a reference compound for laboratory and analytical research and is not for human or animal use.
Melanotan II Research Reference. (2026). Pure Peptides Labs Research Catalogue. Retrieved from https://purepeptideslabs.net/research-catalogue/melanocortin-research-peptides/melanotan-ii/
Materials listed on this platform are supported by independent testing and published documentation for laboratory research contexts.
