PT-141 Chemical Structure, Sequence, and Molecular Properties for Research Use
PT-141 Chemical Structure, Sequence, and Molecular Properties for Research Use
Last Updated: January 15, 2025
Research Use Only Disclaimer: PT-141 (Bremelanotide) is sold exclusively for in vitro laboratory and preclinical research. It is not intended for human or veterinary use, consumption, or self-administration. All technical data on this page is provided for scientific reference only. Compliance with all applicable federal, state, and institutional regulations governing research peptide use is the sole responsibility of the researcher.
Understanding the chemical architecture of a research peptide is not just academic. For laboratory scientists, structural data informs experimental design, buffer selection, reconstitution protocols, receptor binding assay setup, and the interpretation of published preclinical literature. This article provides a thorough technical review of PT-141's (Bremelanotide's) primary structure, physicochemical properties, and structural features relevant to its use as a melanocortin receptor research tool.
PT-141 at a Glance: Key Identifiers
Before going deeper into the chemistry, here is a quick-reference summary of PT-141's primary identifiers used in the scientific literature and regulatory databases:
| Property | Value |
|---|---|
| Common Name | PT-141 |
| INN (International Nonproprietary Name) | Bremelanotide |
| CAS Number | 189691-06-3 |
| Molecular Formula | C₅₀H₆₉N₁₅O₁₀ |
| Molecular Weight | 1025.18 g/mol |
| Peptide Type | Cyclic lactam heptapeptide |
| Amino Acid Count | 7 |
| Appearance (typical) | White to off-white lyophilized powder |
| Solubility | Water-soluble; typically reconstituted in sterile water or dilute acetic acid |
| Storage Form | Lyophilized |
Full Amino Acid Sequence
PT-141's primary sequence is:
Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH
Breaking that down for researchers who may be less familiar with peptide shorthand notation:
- Ac = N-terminal acetyl group (in some literature descriptions this is listed differently, reflecting variation in synthesis protocol reporting)
- Nle = Norleucine, an unnatural amino acid substituted at position 4 (corresponding to methionine in the native alpha-MSH sequence), improving metabolic stability
- Asp = Aspartic acid (provides the carboxyl group for the lactam bridge)
- His = Histidine
- D-Phe = D-Phenylalanine (a stereochemical inversion at this position that increases receptor affinity and resistance to proteolytic degradation)
- Arg = Arginine
- Trp = Tryptophan
- Lys = Lysine (provides the epsilon-amino group for the lactam bridge)
- -OH = Free C-terminal carboxyl
The cyclic lactam bridge forms between the side-chain carboxyl of Asp and the side-chain amine of Lys, constraining the backbone conformation of the peptide.
Understanding the Cyclic Lactam Structure
For researchers new to cyclic peptide chemistry, the cyclic lactam structure of PT-141 is worth a brief explanation because it fundamentally shapes the compound's research-relevant properties.
In a linear peptide, the chain is flexible and can adopt many different three-dimensional shapes in solution. This conformational flexibility can be problematic for receptor binding studies because the active binding conformation may represent only a small fraction of the overall conformational ensemble. It also tends to make the peptide more accessible to proteolytic enzymes, which cleave the peptide backbone.
A lactam bridge addresses both of these issues. By forming a covalent bond between two side chains within the peptide, the cyclic structure locks the backbone into a more restricted set of conformations. In PT-141, the bridge between Asp and Lys creates a cyclic core that holds the His-D-Phe-Arg-Trp pharmacophore in a geometry favorable for melanocortin receptor engagement.
The practical result for in vitro research: PT-141 has better metabolic stability in biological assay matrices than linear melanocortin peptides, and its receptor binding properties are more reproducible because the active conformation is pre-organized.
The Role of Non-Standard Residues in Research Relevance
Two residues in PT-141's sequence deserve special attention because they were deliberately introduced to optimize the compound for research use: Norleucine (Nle) and D-Phenylalanine (D-Phe).
Norleucine at Position 4
In the parent compound alpha-MSH, position 4 is occupied by methionine. Methionine is susceptible to oxidation, which can alter peptide behavior in assay systems and complicates long-term storage stability. Norleucine is a non-proteinogenic amino acid with a similar side chain length but without the oxidation-prone sulfur atom. Substituting Nle for Met at this position was a deliberate SAR decision made in the early Melanotan research program and was retained in PT-141's design.
For laboratory researchers, this means PT-141 is more resistant to oxidative degradation than native melanocortin peptides, an important practical consideration for maintaining consistent assay performance across experiments.
D-Phenylalanine at Position 7
Introducing a D-amino acid at this position serves two research-relevant purposes. First, the stereochemical inversion enhances binding affinity at melanocortin receptors relative to the L-form at this position. Second, D-amino acids are resistant to the enzymatic cleavage by proteases that recognize and cleave L-amino acid sequences. This resistance to proteolysis further extends the useful lifetime of the peptide in biological assay conditions.
Physicochemical Properties Relevant to Lab Work
Molecular Weight and Molar Calculations
PT-141's molecular weight of approximately 1025.18 g/mol is relevant when preparing stock solutions for in vitro work. Researchers preparing molar concentrations should confirm the exact molecular weight from the Certificate of Analysis (COA) provided with their specific lot, as minor variations in peptide modification or salt form can affect the actual mass.
Example molar calculation: To prepare 1 mL of a 1 mM stock solution: - Moles needed = 0.001 L × 0.001 mol/L = 1 × 10⁻⁶ mol - Mass needed = 1 × 10⁻⁶ mol × 1025.18 g/mol = 0.001025 g = 1.025 mg
Solubility Profile
PT-141 is hydrophilic due to its charged residues (Arg, Asp, His, Lys) and is generally soluble in sterile water or phosphate-buffered saline at research-relevant concentrations. For particularly concentrated stock solutions, dilute acetic acid (0.1% to 1%) may be used to assist initial dissolution.
Important note for researchers: avoid alkaline pH conditions when preparing PT-141 solutions, as basic conditions can promote degradation of certain residues. Target pH 5.5 to 7.0 for most aqueous reconstitution applications.
Isoelectric Point (pI)
The pI of PT-141 is estimated in the range of 9 to 10 based on the preponderance of basic residues (His, Arg, Lys). This basic character means that at physiological pH (7.4), PT-141 carries a net positive charge, which influences its behavior in ion-exchange chromatography, gel filtration, and interactions with negatively charged surfaces in laboratory equipment.
Spectroscopic Identification
For researchers performing quality verification of PT-141 preparations in the lab, the following spectroscopic methods are standard:
Mass Spectrometry: The most definitive method for confirming PT-141 identity. Expected [M+H]+ ion: approximately 1026.2 m/z. High-resolution mass spectrometry (HRMS) can confirm exact mass to multiple decimal places.
HPLC Purity Analysis: Reversed-phase HPLC on a C18 column with a water/acetonitrile gradient (with 0.1% TFA) is the standard method for purity determination. Research-grade PT-141 from reputable suppliers should show >98% purity by area under the curve.
UV Absorbance: PT-141 contains tryptophan (Trp), which absorbs strongly at 280 nm, and histidine, which absorbs at around 210-215 nm. UV detection at 214-220 nm is typically used for HPLC analysis.
Structural Comparison: PT-141 vs Closely Related Melanocortin Peptides
| Structural Feature | Alpha-MSH | MT-II | PT-141 |
|---|---|---|---|
| Chain Type | Linear | Cyclic | Cyclic |
| Residue Count | 13 | 7 | 7 |
| Lactam Bridge | No | Yes | Yes |
| D-Phe at position 7 | No | Yes | Yes |
| Nle at position 4 | Variant-dependent | Yes | Yes |
| Molecular Weight (approx.) | ~1664 Da | ~1025 Da | ~1025 Da |
| Proteolytic Stability | Low | High | High |
Why These Molecular Properties Matter for Experimental Design
Knowing PT-141's structural details is directly relevant to several common laboratory applications:
Radioligand Binding Assays: The MW and purity of the reference compound directly affect accurate ligand concentration calculations. Error in concentration translates to error in IC50 or Ki determinations.
Cell-Based cAMP Assays: PT-141's solubility profile and stability at physiological pH mean it performs reliably in cell-based signaling assays when freshly diluted from stock, though freeze-thaw cycles of working solutions should be minimized.
Peptide Stability Studies: Researchers using PT-141 as a stability reference compound benefit from understanding which structural elements (the cyclic core, Nle, D-Phe) contribute to its resistance to degradation, allowing appropriate controls to be designed.
Custom Peptide Synthesis Reference: For labs synthesizing structural analogs of PT-141, the published sequence provides a scaffold for SAR exploration.
Related Research Resources in This Cluster
- Palmetto Peptides Guide to the Research Peptide PT-141 (Bremelanotide)
- History of PT-141 Research Peptide: From Melanotan II Discoveries to Modern Laboratory Applications
- PT-141 Mechanism of Action as a Melanocortin Receptor Agonist in Preclinical Research
- PT-141 vs Melanotan II: Comparative Analysis for Research Peptide Applications
- Using PT-141 in Radioligand Binding and Cell-Based Receptor Assays: A Research Applications Guide
- PT-141 Structure-Activity Relationships: How Molecular Modifications Affect Melanocortin Receptor Research Outcomes
Frequently Asked Questions
Q: What is the molecular formula of PT-141 (Bremelanotide)? The molecular formula is C₅₀H₆₉N₁₅O₁₀, with a molecular weight of approximately 1025.18 g/mol. Always confirm exact MW from the Certificate of Analysis for your specific lot.
Q: What is the amino acid sequence of PT-141? Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. It is a cyclic heptapeptide with a lactam bridge between aspartate and lysine side chains, incorporating norleucine and D-phenylalanine as non-standard residues.
Q: Is PT-141 water-soluble for laboratory use? Yes, generally water-soluble at research concentrations. Reconstitute in sterile water or PBS. For concentrated stocks, dilute acetic acid (0.1-1%) may assist dissolution. Target pH 5.5-7.0.
Q: Why does PT-141 contain D-phenylalanine? D-Phe at position 7 enhances melanocortin receptor binding affinity and provides resistance to proteolytic cleavage, improving stability in biological assay matrices.
Q: What is the CAS number for PT-141? CAS 189691-06-3. This can be used to identify PT-141 (Bremelanotide) in chemical databases and regulatory references.
Citations
Hruby VJ, Lu D, Sharma SD, et al. "Cyclic lactam alpha-melanotropin analogues." Journal of Medicinal Chemistry. 1995;38(18):3454-3461.
Dorr RT, Lines R, Levine N, et al. "Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide." Life Sciences. 1996;58(20):1777-1784.
Ewing GW. "The structure-activity relationships of the melanocortin peptides." Journal of Peptide Science. 2010;16:1-12.
Wikberg JE. "Melanocortin receptors: perspectives for novel drugs." European Journal of Pharmacology. 1999;375(1-3):295-310.
Todorovic A, et al. "Synthesis and characterization of cyclic melanocortin peptide analogs." Peptides. 2005;26:2352-2359.
Author: Palmetto Peptides Research Team
This article is provided for educational and scientific reference only. PT-141 (Bremelanotide) is sold exclusively as a research peptide for qualified laboratory use. Not intended for human or veterinary use, administration, or therapeutic application. Researchers are responsible for compliance with all applicable regulations.
Part of the PT-141 Research Guide — Palmetto Peptides comprehensive research resource.