PT-141 (Bremelanotide): Chemistry Profile & Research Overview

What Is PT-141?

PT-141 is a synthetic cyclic heptapeptide assigned CAS number 189691-06-3, with the structural framework Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. It is a cyclic, lactam-bridged analog of alpha-melanocyte-stimulating hormone (alpha-MSH), developed through systematic structure-activity research on the melanocortin receptor pharmacophore. The defining structural feature is a side-chain-to-side-chain lactam bridge between Asp and Lys, which constrains the conserved His-D-Phe-Arg-Trp “message sequence” into a binding-competent conformation. As a research-grade synthetic peptide, PT-141 is used as a reference compound in melanocortin receptor binding assays, in cyclic-peptide synthesis methodology research, and in structure-activity studies of short, constrained alpha-MSH analogs.

Chemical Properties

Historical Development and Discovery

The PT-141 sequence emerged in the late 1990s from a structure-activity research program at Palatin Technologies on cyclic analogs of alpha-MSH. The program built on earlier published work demonstrating that the central His-D-Phe-Arg-Trp tetrapeptide is the minimal “message sequence” required for melanocortin receptor recognition, and that constraining this sequence into a turn conformation via side-chain cyclization improves both potency and receptor-subtype selectivity in research assays. Investigators systematically varied the ring size, the N-terminal cap, and the residues flanking the message sequence to identify a heptapeptide framework that retained binding while resisting proteolytic cleavage. The resulting compound entered the chemical literature under the development code PT-141 and the INN bremelanotide. It has since become a reference standard in cyclic-peptide methodology and melanocortin receptor research.

Chemical Architecture and Structural Features

The Lactam Bridge and Conformational Constraint

The defining structural feature of PT-141 is a side-chain-to-side-chain lactam bridge connecting the carboxyl group of Asp to the epsilon-amine of Lys. This 23-atom ring constrains the central His-D-Phe-Arg-Trp message sequence into a beta-turn-like conformation that mimics the receptor-bound geometry of native alpha-MSH. Cyclization in this manner is a well-established medicinal-chemistry strategy for improving peptide potency, selectivity, and metabolic stability, and has been applied across many GPCR ligand families.

The D-Phenylalanine Substitution

The D-Phe residue at position 4 of the cyclic core is a substitution from the native L-Phe of alpha-MSH. The D-configuration at this position is a recognized strategy for stabilizing the turn conformation and conferring resistance to chymotrypsin-like proteases. The Nle (norleucine) cap at the N-terminus replaces the native Met, removing a potential oxidation site at the sulfur atom.

Solid-Phase Synthesis Considerations

PT-141 is produced by Fmoc-based solid-phase peptide synthesis (SPPS) with orthogonal protection on the Asp and Lys side chains to permit on-resin lactam bridge formation prior to global deprotection and cleavage. Common challenges discussed in the cyclic-peptide synthesis literature include incomplete ring closure (addressed via high-dilution coupling conditions or pre-cyclization in solution), aspartimide formation at the Asp-His junction, and the orthogonal selection of side-chain protecting groups to permit selective deprotection of the Asp and Lys side chains.

Research Mechanisms

In published research, PT-141 has been characterized as a cyclic agonist of the melanocortin receptor family (MC1R-MC5R), with research-grade binding profiles that differ across the receptor subtypes. The compound is widely used as a reference standard in melanocortin receptor binding and functional assays, in cyclic-peptide methodology research, and in structure-activity studies of constrained alpha-MSH analogs. ITide Labs supplies PT-141 as a research-grade reference compound for these applications.

Research Areas

• Melanocortin receptor (MC1R-MC5R) binding and functional assay methodology
• Cyclic-peptide synthesis methodology research, including on-resin lactam formation
• Structure-activity research on alpha-MSH analogs and the His-D-Phe-Arg-Trp message sequence
• Comparative research with linear alpha-MSH analogs in protease-stability studies
• Reference standard in analytical method development (HPLC-UV, LC-MS)

Quality Assurance

ITide Labs releases each lot of PT-141 against an independent third-party Certificate of Analysis. Lot-specific COAs are published on the corresponding product page once analysis is complete. Identity is confirmed by LC-MS, purity by RP-HPLC-UV, and endotoxin levels by kinetic chromogenic LAL assay. Lyophilized material is stored at 2–8 °C protected from light and is supplied with batch-specific documentation.

Frequently Asked Questions

What is the CAS number for PT-141?

The CAS number for PT-141 (bremelanotide) is 189691-06-3.

What is the molecular weight of PT-141?

The molecular weight of PT-141 is 1025.18 g/mol. The empirical formula is C₅₀H₆₈N₁₄O₁₀.

What is the structural framework of PT-141?

PT-141 has the framework Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, a cyclic heptapeptide with a side-chain lactam bridge between Asp and Lys constraining the central His-D-Phe-Arg-Trp message sequence.

How does PT-141 differ from native alpha-MSH?

PT-141 differs from native alpha-MSH by three modifications: a cyclic constraint via the Asp-Lys lactam bridge, a D-phenylalanine substitution at position 4 of the cyclic core, and an N-terminal Nle (norleucine) replacing Met to eliminate a potential oxidation site.

What is the development code for PT-141?

PT-141 was originally the development code itself, used by Palatin Technologies during structure-activity research. The INN assigned to the compound is bremelanotide.

Why is PT-141 used in research?

PT-141 is used as a reference standard in melanocortin receptor binding and functional assay methodology, in cyclic-peptide synthesis methodology research, and as a model compound for structure-activity research on constrained alpha-MSH analogs.

What is the role of the D-Phe substitution in PT-141?

The D-phenylalanine at position 4 of the cyclic core stabilizes the turn conformation of the bound peptide and confers resistance to chymotrypsin-like proteases that recognize L-Phe at this position.

What laboratory storage does PT-141 require?

Lyophilized PT-141 should be stored at 2–8 °C protected from light for short-term storage and at –20 °C for long-term storage. Reconstituted solutions should be aliquoted and stored frozen.

Is PT-141 a peptide or a small molecule?

PT-141 is a cyclic peptide. At 1025 g/mol it falls clearly in the peptide range, although the lactam-bridged cyclic framework gives it a more constrained, rigid conformation than typical linear peptides.

Is PT-141 available in different sizes from ITide Labs?

ITide Labs currently supplies PT-141 as a 10 mg lyophilized lot. Lot-specific Certificates of Analysis are published on the product page once independent third-party characterization is complete.

Citation

ITide Labs. PT-141 (Bremelanotide): Chemistry Profile and Research Overview. Las Vegas, NV: ITide Labs LLC; 2026.