PT-141

PT-141, also known as bremelanotide, is a synthetic cyclic heptapeptide of the melanocortin family. Its defining structural feature is a side-chain-to-side-chain lactam bridge that closes the molecule into a ring, together with two residues that do not occur in ribosomally synthesised proteins.

Identity and classification

PT-141 derives from the α-melanocyte-stimulating hormone pharmacophore. Its systematic description is Ac-Nle⁴, Asp⁵, D-Phe⁷, Lys¹⁰-cyclo-α-MSH(4–10) — which reads as a compressed account of exactly how the native hormone fragment was modified to produce it. It is catalogued as a melanocortin receptor agonist.

Structure

The molecule is written Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. Four features are worth separating out:

• The lactam bridge. An amide bond between the aspartate side-chain carboxyl and the lysine side-chain amine closes residues 2 through 7 into a macrocycle. This is a side-chain-to-side-chain cyclisation, not a head-to-tail one, and it is what constrains the His-D-Phe-Arg-Trp core into the conformation the melanocortin receptors recognise.
• Norleucine in place of methionine. Nle is an unbranched six-carbon residue isosteric with Met but with no sulfur — a deliberate substitution that removes the oxidation liability entirely.
• D-phenylalanine at the position corresponding to Phe7 of the native hormone. Inverting the stereocentre confers protease resistance and locks the aromatic side chain.
• Free C-terminal acid. The chain terminates in –OH.

The melanotan II distinction

PT-141 and melanotan II share an identical cyclic core and differ at exactly one position: the C-terminus. PT-141 ends in a free acid; melanotan II ends in a carboxamide. The difference is the substitution of –OH for –NH₂, approximately 1 Da.

Because the difference is a single dalton on a molecule of a thousand, low-resolution mass spectrometry does not reliably distinguish them, and supplier listings confuse the two routinely. The two are separable by reverse-phase chromatography — the amide is marginally more retained — and definitively distinguished by high-resolution MS. If a certificate reports both compounds’ masses as the same figure, it has not distinguished them.

Specification and characterisation

• RP-HPLC purity at 214 nm, with 280 nm as a useful second channel: the single tryptophan gives strong aromatic absorbance, and the Trp:backbone ratio is itself a compositional check.
• High-resolution mass confirmation against 1025.2 average, 1024.52 monoisotopic. As above, resolution matters here more than it does for most peptides in this catalogue.
• Ring closure. The characteristic synthesis-related impurity is the linear (uncyclised) precursor, which differs from the cyclic product by +18 Da — the water lost on amide formation. It is mass-resolvable and is the impurity a certificate for a cyclic peptide ought to address.
• Tryptophan-related degradation. Trp is the most photolabile of the standard residues and oxidises to N-formylkynurenine and kynurenine on light exposure. Protection from light is not a generic precaution for this molecule; it is specific.
• Counter-ion and net peptide content. Commonly supplied as the acetate; the registry number above is the free peptide.

Handling and stability

Store sealed at 2–8 °C, dry, in the dark. Light protection is the primary handling requirement because of the tryptophan. There is no cysteine and no methionine — the norleucine substitution deliberately removed the sulfur — so oxidation of the kind that limits methionine-containing peptides does not apply here, and the constrained macrocycle is conformationally stable.

Equilibrate in a desiccator before opening.

Related compounds in this library

Melanotan II — the C-terminal amide counterpart, as above. Both are cyclic melanocortin peptides built on the same core. KPV is also α-MSH-derived but is a linear tripeptide fragment from the opposite end of the hormone and shares no structural motif with either.

References

Chemical, specification and analytical sources. This list is deliberately limited to chemistry and analytical references.

• PubChem CID 9941379, bremelanotide — formula, molecular weight, structure
• Chemsrc, CAS 189691-06-3 — registry and mass data
• BOC Sciences, bremelanotide record — formula and mass confirmation
• Bachem, Handling and Storage Guidelines for Peptides — tryptophan photolability, lyophilised solid handling

Cosmic Aminos supplies this material as a laboratory reagent for in-vitro research use only. It is not a drug, food, cosmetic or dietary supplement, is not approved by the Food and Drug Administration for any use, and is not for human or veterinary consumption. No dosing, administration or preparation guidance is provided.