“These Statements Have Not Been Evaluated By The Food And Drug Administration.
This Product Is Not Intended To Diagnose, Treat, Cure Or Prevent Any Disease.”
Melanotan 2 (Cyclic Heptapeptide Lactam)
PRODUCT SPECIFICATIONS
- Chemical Name: Ac-Nle-cyclo-NH2
- Systematic Name: N-acetyl-L-norleucyl-L-aspartyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-L-lysinamide (2→7)-lactam.
- Peptide Classification: Synthetic cyclic lactam analogue of alpha-melanocyte-stimulating hormone ($alpha$-MSH).
- Peptide Type: Non-selective melanocortin receptor agonist.
- Molecular Formula: $C_{50}H_{69}N_{15}O_{9}$
- Molecular Weight: 1024.2 g/mol
- CAS Registry Number: 121062-08-6
- Purity: $ge98%$ (HPLC verified; specifically tested for D-Phe7 racemization impurities).
- Solubility: Soluble in sterile water and dilute acetic acid; stability is pH-dependent.
- Storage: Lyophilized powder at $-20 C, protected from light and moisture.
- Molecular Structure: Features a critical lactam bridge between Asp5 and Lys10 residues to stabilize the reverse-turn conformation.
Disclaimer
For Research Use Only (RUO). Not for human or veterinary use. Not for cosmetic application.
DESCRIPTION
Melanotan 2 is a superpotent melanocortin analog developed to overcome the rapid enzymatic degradation of natural $alpha$-MSH. Through rational drug design, the inclusion of D-Phenylalanine (D-Phe) at position 7 and the formation of a covalent lactam bridge between Aspartic Acid (residue 5) and Lysine (residue 10) constrain the peptide into a rigid beta-turn conformation.
This structural modification significantly increases its binding affinity (Ki) across multiple melanocortin receptor subtypes, specifically MC1R (pigmentation) and MC4R (energy homeostasis and neuro-signaling).
In the research context, Melanotan 2 serves as a critical probe for mapping the central melanocortin system. It is extensively utilized to study the pathophysiology of energy balance, the regulation of tyrosinase activity in melanocytes, and the hemodynamic effects of sympathomimetic activation. Due to its ability to cross the blood-brain barrier in animal models, it remains a primary tool for investigating neuro-mediated physiological responses.
EXPERIMENTAL & ANALYTICAL USE
Melanotan 2 is utilized in laboratory research for:
Receptor Kinetics : Determining binding constants (Ki) and signal transduction efficacy at MC1R vs. MC4R interfaces.
Metabolic Signaling : Investigating lipolysis and appetite suppression pathways in rodent obesity models.
Toxicology Modeling : Studying the mechanisms of sympathomimetic toxicity, renal vasoconstriction, and rhabdomyolysis in high-dose scenarios.
Neurophysiology : exploring the role of MC4R activation in CNS arousal and thermoregulation.
Analytical Calibration : Serving as a reference standard for LC-MS/MS detection of peptide impurities and metabolites in forensic toxicology.
TOXICOLOGY AND DETECTION METHODS
For forensic and anti-doping research, Melanotan 2 is identified in biological matrices using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
Primary Analyte : The intact parent peptide is monitored using the doubly charged precursor ion $[M+2H]^{2+}$ at m/z 513.
Metabolite Profile : Research indicates Melanotan 2 resists rapid hydrolysis due to the lactam bridge, but metabolites resulting from deamidation and C-terminal cleavage can be detected.
Adverse Event Mechanisms : Investigational models use MT-II to study renal infarction pathways, specifically hypothesizing that non-selective MCR activation triggers severe sympathetic vasoconstriction and thrombotic microangiopathy in renal vasculature.
These analytical methods are used exclusively for forensic, anti-doping, and laboratory toxicology research.
HANDLING AND STABILITY
Melanotan 2 is supplied as a lyophilized white powder (acetate salt).
Reconstitution : Soluble in sterile bacteriostatic water. However, for extended stability during assays, reconstitution in dilute acetic acid (0.1%) is often preferred to prevent base-catalyzed deamidation.
Lactam Bridge Sensitivity : While the cyclic structure confers serum stability, the peptide is sensitive to hydrolysis at extreme pH. Avoid repeated freeze-thaw cycles which can disrupt the conformational integrity.
Storage : Lyophilized vials must be stored at $-20^{circ}C$. Reconstituted aliquots should be used immediately or stored at $-80^{circ}C$.
RESEARCH USE ONLY
MOLECULAR & TECHNICAL CHARACTERISTICS
Melanotan 2 is synthesized using Solid Phase Peptide Synthesis (SPPS) and purified to eliminate synthesis-related impurities, specifically:
Stereochemical Purity : Rigorous testing to ensure the D-Phe7 residue has not racemized during synthesis, which would alter receptor selectivity.
Impurity Profile : Elimination of “failure sequences” and aspartimide byproducts often found in lower-grade preparations.
Stability : The N-acetyl and C-amidated termini provide resistance to exopeptidases, making it suitable for prolonged in vivo animal studies compared to linear peptides.
SCIENTIFIC SIGNIFICANCE
The study of Melanotan 2 contributes to the broader understanding of:
GPCR Pharmacology : Ligand-receptor interaction dynamics of Class A G-Protein Coupled Receptors.
Sympathetic Nervous System : The role of melanocortins in blood pressure regulation and renal hemodynamics.
Immunogenicity : The FDA has flagged Melanotan 2 for potential immunogenicity risks (development of anti-drug antibodies) due to peptide aggregation, making it a subject of interest for immunological safety research.
RUO COMPLIANCE
All experimental applications of Melanotan 2 are conducted under Research Use Only (RUO) protocols.
FDA Status : Placed on the 503A Bulks List Category 2 (Significant Safety Risks) as of late 2023/2024. It is strictly prohibited for use in compounding for human administration.
WADA Status : Explicitly prohibited under Section S2 (Peptide Hormones).
Intended Use : Not for diagnostic, therapeutic, cosmetic, or veterinary purposes.
FEATURES / HIGHLIGHTS
- Potent, non-selective agonist of MC1R, MC3R, MC4R, and MC5R.
- Cyclic heptapeptide structure with verified lactam bridge integrity.
- Enables investigation into sympathomimetic toxicity and renal pathophysiology.
- Verified $ge98%$ purity via HPLC to minimize D-Phe7 racemization.
- High stability profile compared to linear $alpha$-MSH.
Strictly designed and labeled for Research Use Only (RUO).
