PT-141 vs MT-2: How Bremelanotide and Melanotan II Differ

Same ring, different ending

MT-2 came out of a 1980s University of Arizona program that designed cyclic lactam analogs of alpha-melanocyte-stimulating hormone (alpha-MSH). A lactam bridge between an aspartic acid and a lysine side chain closes the core into a ring, and norleucine and D-phenylalanine replace the native methionine and L-phenylalanine ^[1].

PT-141, also called bremelanotide, keeps that exact ring. The difference is the last group: MT-2 is a C-terminal amide (-NH2), while PT-141 ends in a free carboxylic acid (-OH). Reviews of melanocortin ligands list both as synthetic alpha-MSH analogs ^[4].

Structure and mass at a glance

• MT-2: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2, formula C50H69N15O9, listed molecular weight 1024.2 Da, monoisotopic mass about 1023.540 Da.
• PT-141: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, formula C50H68N14O10, listed molecular weight 1025.2 Da, monoisotopic mass about 1024.524 Da.
• The difference: swapping -NH2 for -OH removes one nitrogen and one hydrogen and adds one oxygen, a net change of about +0.984 Da. Everything else, including the His-D-Phe-Arg-Trp core, is identical.

What the receptor literature examines

Melanocortin research describes five receptor subtypes, MC1R through MC5R. Binding studies in cells expressing the human MC1, MC3, MC4 and MC5 receptors used MT-II as a reference cyclic lactam and found the cyclic lactams had higher overall affinity than cyclic disulfide analogs ^[2]. In a cell model expressing MC4R, MT-II produced a cAMP signal that persisted for at least an hour after the compound was washed out, unlike alpha-MSH ^[3].

A 2019 development review describes bremelanotide as a synthetic alpha-MSH analog with high affinity for MC4R ^[5]. Bremelanotide was also developed as a regulated pharmaceutical product; research-grade material is a different thing, and nothing on this page concerns use in people. The PT-141 and MT-2 research overviews summarize the receptor literature with citations.

Why a basic mass check is not enough

Because the two molecules differ by less than 1 Da, a low-resolution mass spectrum can be misleading. The [M+H]+ ions sit near m/z 1024.55 for MT-2 and 1025.53 for PT-141, and the natural carbon-13 isotope peak of MT-2 lands only about 0.02 Da from the main PT-141 peak. Separating them by mass alone takes high-resolution instruments.

A forensic study used LC with high-resolution Orbitrap mass spectrometry, accurate-mass isotope patterns and fragment ions to characterize MT-II and bremelanotide in unknown seized samples, which shows the level of analysis needed to tell them apart with confidence ^[6].

Chromatography helps too. The free acid on PT-141 changes its charge with pH, so on reversed-phase HPLC under acidic conditions the two usually elute at different times.

A degradation link worth knowing

Hydrolysis of MT-2's C-terminal amide would give a molecule with PT-141's structure. So a small peak at the PT-141 mass in MT-2 material can be a degradation product, not necessarily a mix-up. Dry, frozen, sealed storage limits hydrolysis, and the storage and degradation guide covers the chemistry.

The sequence notation guide explains how the -NH2 and -OH suffixes and the cyclo[ ] brackets in these names are read.

Handling notes

Both are supplied as Lyophilized powders and stored sealed and frozen. Tryptophan in the ring is light-sensitive, so limiting light exposure is common practice. For solution arithmetic with each listed molecular weight, see the PT-141 and MT-2 calculators, and MT-1 vs MT-2 compares the linear analog.