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PT-141 Chemical Structure, Sequence, and Molecular Properties for Research Use | Palmetto Peptides

PT-141 Chemical Structure, Sequence, and Molecular Properties for Research Use Research Notice: This article covers research on PT-141 research peptide and Melanotan II (MT-2) research peptide — available from Palmetto Peptides for laboratory use only. Last Up

By Recovery & Performance Peptides Editorial Team

PT-141 Chemical Structure, Sequence, and Molecular Properties for Research Use

Research Notice: This article covers research on PT-141 research peptide and Melanotan II (MT-2) research peptide — available from Palmetto Peptides for laboratory use only.

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.

Last Updated: April 6, 2026 | Reading Time: Approximately 8 minutes | Author: Palmetto Peptides Research Team

Quick Answer

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.

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:

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

Chain Type

Linear

Cyclic

Residue Count

13

Lactam Bridge

No

Yes

D-Phe at position 7

Nle at position 4

Variant-dependent

Molecular Weight (approx.)

~1664 Da

~1025 Da

Proteolytic Stability

Low

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.

Related research: MT-2 Melanotan II research, MT-2 melanocortin receptor mechanism, and MT-2 laboratory applications.

CONNECTED / MODULES

Post-session references

Selected from shared article topics. Source links are retained where available.

01

Handling & safety lane

Source-derived education, not individual medical guidance or an instruction to dose.

DOSAGE SOURCE

PT-141 HSDD Dosing, Administration, and Pharmacokinetics

PT-141 for HSDD is administered as a 1.75mg subcutaneous injection into the abdomen or thigh at least 45 minutes before anticipated sexual activity. The peptide reaches peak plasma concentration (Cmax) approximately 1 hour post-injection with a mean half-life of 2.7 hours. Sexual desire effects peak within 1–3 hours and diminish by 6 hours post-administration. Maximum recommended dosing frequency is one injection per 24 hours, with no more than 8 doses per month. The peptide structure is a cyclic heptapeptide analog of α-MSH with the sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. Unlike linear peptides susceptible to rapid proteolytic degradation, the cyclic structure confers enzymatic stability and allows subcutaneous bioavailability sufficient for CNS receptor engagement. Bremelanotide does not cross the blood-brain barrier in substantial concentrations—instead, it acts on melanocortin receptors in circumventricular organs (regions lacking a complete blood-brain barrier) and possibly through vagal afferent pathways that relay signals centrally. Patients using PT-141 HSDD therapy must be counseled on injection technique, site rotation to prevent lipohypertrophy, and proper disposal of sharps. The medication is supplied as a lyophilized powder requiring reconstitution with bacteriostatic water or as a pre-filled autoinjector pen. Once reconstituted, vials must be stored at 2–8°C and used within 28 days—temperature excursions above 8°C cause irreversible protein denatur…
SIDE EFFECTS

PT-141 Side Effects — What Research Reveals | Real Peptides

PT-141 (bremelanotide) produces nausea in roughly half of all research subjects during the first three administrations. Not because of contamination or improper reconstitution, but because the melanocortin receptor pathway it activates directly influences brainstem nausea centers. This isn't a sign the peptide is working poorly. It's evidence the mechanism is engaging exactly where it should. The challenge for researchers isn't whether PT-141 side effects will occur. It's understanding which ones signal normal receptor activation versus which require protocol modification. We've analyzed hundreds of research protocols involving PT-141 across diverse study populations. The gap between successful completion and early discontinuation comes down to three factors most study designs never address upfront: pre-administration cardiovascular screening, titration schedules that account for melanocortin receptor density variation, and differentiation between transient receptor-mediated effects versus persistent adverse events requiring intervention. What are the most common PT-141 side effects observed in research settings? PT-141 side effects include nausea (40–50% incidence), facial flushing (25–35%), headache (15–25%), and transient blood pressure elevation (10–15 mmHg systolic increases documented in Phase 2 trials). These effects typically peak 60–90 minutes post-administration and resolve within 4–6 hours without intervention. The melanocortin receptor pathway mediates both the i…
02

Question drills

Open a question for its connected answer.

01What If the Subject Has Concurrent SSRI Use?+

Selective serotonin reuptake inhibitors (SSRIs) are known to blunt orgasmic response through 5-HT2A receptor overactivation and downstream suppression of dopaminergic signaling. The exact pathway PT-141 enhances. Research suggests PT-141 may partially overcome SSRI-induced sexual dysfunction by bypassing serotonergic interference and directly activating melanocortin-dopamine circuits. Document baseline sexual function scores before SSRI initiation if possible, as this allows attribution of improvements to PT-141 versus natural SSRI adaptation. Concurrent use is not contraindicated, but effects may be attenuated compared to SSRI-naive subjects.

SOURCE / realpeptides.co ↗
02What If a Patient Has Low Libido but Normal Erectile Function?+

Administer PT-141, not tadalafil. The pt-141 vs cialis mechanism split means tadalafil will sustain an erection only if arousal and desire are already present. It does not initiate desire. If the patient reports reduced interest in sexual activity but can achieve firm erections when motivated, the bottleneck is central (hypothalamic/dopaminergic), not peripheral (vascular). PT-141's melanocortin receptor activation addresses this directly. Tadalafil in this scenario adds vascular capacity the patient does not need and will not improve subjective arousal.

SOURCE / realpeptides.co ↗
03What If I Experience Nausea After PT-141 Injection?+

Pre-treat with ondansetron 4 mg orally 30 minutes before bremelanotide administration. Nausea occurs because MC4R activation in the area postrema (the brainstem's vomiting center) is unavoidable with systemic melanocortin agonists. Ondansetron blocks serotonin 5-HT3 receptors in the same region, preventing nausea without interfering with hypothalamic MC4R activity. The desire effect remains intact while the adverse event is eliminated. Clinical data show this approach reduces nausea incidence from 40% to under 10%.

SOURCE / realpeptides.co ↗
04What If PT-141 Is Combined with Behavioural Therapy or Topical Anaesthetics?+

Combination protocols are an active area of investigation. Pairing PT-141 with start-stop techniques or squeeze methods could theoretically amplify behavioural gains by providing a pharmacological safety margin during ejaculatory threshold learning. Topical anaesthetics pose a different question: since PT-141 works centrally and lidocaine works peripherally, the mechanisms don't overlap. But reducing penile sensation while simultaneously enhancing arousal through melanocortin pathways might create a mismatch between desire and sensation that some patients find uncomfortable. No published trials have tested this combination, but anecdotal reports from early-phase studies suggest that patients using both PT-141 and topical agents reported subjective dissatisfaction with reduced tactile feedback despite extended IELT.

SOURCE / realpeptides.co ↗
05What If PT-141 Stops Working After Several Months of Use?+

Tachyphylaxis. Progressive loss of efficacy with repeated dosing. Has not been documented in controlled trials of PT-141 for hypoactive sexual desire, but clinical experience suggests some patients report diminished subjective effect after 6 to 12 months of regular use. This may reflect melanocortin receptor downregulation, psychological habituation to the drug's effects, or progression of the underlying desire disorder. A structured washout period (4 to 8 weeks without dosing) sometimes restores initial response magnitude, though this is anecdotal rather than evidence-based. If efficacy loss occurs despite washout, reassess whether the original diagnosis of centrally-mediated HSDD remains accurate or whether relational, situational, or mood factors have emerged as primary contributors.

SOURCE / realpeptides.co ↗
03

Evidence cooldown

Research context and source excerpts for a slower second read.

RESEARCH

The Brain-Imaging Evidence: Watching the Neuroendocrine Effect

If the RECONNECT trials showed that bremelanotide improves self-reported desire, a later functional-MRI study offered a mechanistic look at how — and it is the most direct human evidence that the effect is genuinely central and neuroendocrine rather than peripheral or purely subjective. In a randomized, double-blind, placebo-controlled crossover study, 31 premenopausal women with HSDD underwent functional MRI while viewing erotic visual stimuli, on separate occasions after receiving 1.75 mg subcutaneous bremelanotide or placebo.8 MC4R agonism significantly increased participant-reported sexual desire compared with placebo for up to 24 hours, and, critically, it altered brain activation in regions involved in sexual processing — providing objective neural correlates for the subjective effect. This was the first trial to image the effect of MC4R agonism on sexual brain processing in women with HSDD.8 The imaging study matters for the title’s framing in two ways. It substantiates the “neuroendocrine pathways” claim with direct evidence that the drug changes activity in central sexual-processing circuits, not merely in the periphery. And it reinforces the boundary of what has been demonstrated: the measured outcome was sexual brain processing and desire, imaged under erotic stimuli. The study offers no read-out on generalized energy, alertness, or fatigue, and it should not be cited — as it sometimes is — as evidence that the drug “activates the brain” in some diffuse, energizing way. It activated sexual-processing circuitry in a desire-disorder population, which is a specific and appropriately narrow finding.

RESEARCH

Research Quality Parameters

PT-141 for gonadal biology research is typically supplied at ≥98% purity (RP-HPLC) with mass confirmation by ESI-MS ([M+H]⁺ ~1025.2 Da for the cyclic peptide). Endotoxin testing (LAL ≤0.1 EU/mg) is essential for steroidogenesis assays where LPS contamination alters cAMP and steroidogenic enzyme expression. MC3R/MC4R antagonists (SHU9119, MTII-NH2, HS014) at receptor-selective concentrations are required as pharmacological controls. For Leydig cell work, LH and ACTH positive controls are mandatory to establish the magnitude of gonadotrophin- and ACTH-driven steroidogenesis as reference points. Protein measurement in steroidogenesis assays (Bradford or BCA) and steroid quantification by LC-MS/MS (rather than ELISA alone) improve quantitative accuracy. The cyclic peptide structure of PT-141 confers enhanced proteolytic stability relative to linear melanocortin analogues — reconstituted solutions are stable at 4°C for 2–4 weeks if sterile-filtered and protected from light.

05

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