Melanotan II (MT2)

Melanotan 2 Peptide Overview

Melanotan 2 (MT-II) is a synthetic, high-potency derivative of alpha-melanocyte-stimulating hormone (alpha-MSH). This peptide was developed as part of a targeted effort to find a "sunless" tanning agent that could mitigate the risk of skin cancer by increasing protective melanin levels. Through advanced peptide engineering, researchers created a cyclic version of the hormone that is significantly more effective at binding to melanocortin receptors than its natural precursor.

MT-II has since become a focal point for diverse biological research. It is uniquely capable of crossing the blood-brain barrier, allowing it to modulate receptors in the central nervous system. This capability has opened doors for studies on its role in energy metabolism, libido, and even complex social behaviors. Its ability to act on several physiological fronts makes it one of the most studied peptides in contemporary pharmacology.

Melanotan 2 Peptide Structure

The molecular design of Melanotan 2 focuses on durability and receptor affinity. By forming a cyclic bridge between specific amino acids, the peptide maintains a "locked" shape that fits perfectly into the melanocortin receptor sites.

Chemical Formula:

C50H69N15O9

Molecular Composition:

This heptapeptide consists of seven amino acids: Norleucine, Aspartic Acid, Histidine, D-Phenylalanine, Arginine, Tryptophan, and Lysine.

Structure Solution Formula:

Cyclic(Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys)-NH2

The substitution of Norleucine for Methionine ensures the peptide is resistant to oxidation, while the D-isomer of Phenylalanine provides defense against enzymatic breakdown in biological environments.

Melanotan 2 Peptide Research

Melanocortin Receptor Dynamics

Melanotan 2 interacts with the melanocortin system to produce systemic effects. The following table summarizes the primary research areas associated with each receptor:

Receptor Subtype

Main Functions

Research Implications

MC1R

Melanin synthesis

Skin protection and tanning research

MC3R

Cardiovascular signaling

Heart rate and blood pressure regulation

MC4R

CNS arousal and satiety

Obesity, ED, and addiction research

MC5R

Lipid and glucose metabolism

Diabetes and metabolic syndrome studies

Social Cognition and Autism

Current research explores MT-II as a potential tool for addressing social deficits in neurodevelopmental conditions. In models of Autism Spectrum Disorder, MT-II has been shown to improve social bonding and communication. It is believed that by stimulating the MC4R pathway, the peptide triggers a cascade that increases oxytocin levels, a hormone essential for social interaction.

Obesity and Food Intake Preference

Melanotan 2 has been observed to drastically alter feeding behavior in laboratory subjects. By activating the MC4R receptor in the hypothalamus, MT-II reduces the desire for food and increases energy expenditure. Research shows that it specifically decreases the craving for high-fat diets, suggesting it may play a role in identifying the neural pathways involved in food addiction and binge eating disorders.

Sexual Health and Central Arousal

While many treatments for sexual dysfunction focus on the vascular system, MT-II research focuses on the brain's arousal centers. MT-II has been shown to effectively induce an erectile response in subjects who do not respond to traditional PDE5 inhibitors. This indicates that the melanocortin system is a primary driver of sexual desire and physical response, regardless of the vascular state.

Glucose Regulation and Diabetic Studies

Melanotan 2 contributes to the regulation of glucose through pathways that do not require insulin. Research suggests that the peptide can lower blood sugar levels by signaling the brain to reduce hepatic glucose production and increase the rate at which cells consume glucose. This makes it an important subject for investigating alternative management strategies for type 2 diabetes.

Addiction and Impulse Control

MT-II's influence extends to the regulation of addictive behaviors. Studies involving alcohol consumption in rodents have shown that MT-II reduces the intake of ethanol and decreases the motivation to seek out the substance. This research suggests that the melanocortin system is deeply involved in the brain's reward and impulse-control mechanisms.

Article Author

This research summary was compiled by Dr. Mac E. Hadley, Ph.D. As a leading figure in the discovery of melanotropic peptides, Dr. Hadley's work provided the foundation for the entire field of melanocortin research. His expertise in peptide synthesis and pharmacology helped bridge the gap between basic laboratory science and complex physiological application.

Scientific Journal Author

The primary data regarding Melanotan 2 were established by Dr. Hadley in collaboration with Dr. Victor J. Hruby and Dr. Stephen H. King. Their work, published in major scientific journals such as Life Sciences and the International Journal of Impotence Research, remains the definitive source for understanding the cyclic structure and receptor affinity of MT-II.

Reference Citations

1. Ryakhovsky, Vladimir V et al. "The first preparative solution phase synthesis of Melanotan II." Beilstein Journal of Organic Chemistry vol. 4 (2008): 39.
2. Mac E. Hadley, "Discovery that a melanocortin regulates sexual functions in male and female humans," Peptides, Volume 26, Issue 10, 2005, Pages 1687-1689.
3. King, Stephen H et al. "Melanocortin receptors, melanotropic peptides and penile erection." Current topics in medicinal chemistry vol. 7, 11 (2007): 1098-1106.
4. Peters, Bjorn, et al. "Melanotan II: a possible cause of renal infarction: review of the literature and case report." CEN case reports vol. 9, 2 (2020): 159-161.
5. Ter Laak, Mariel P, et al. "The potent melanocortin receptor agonist melanotan-II promotes peripheral nerve regeneration and has neuroprotective properties in the rat." European Journal of Pharmacology vol. 462, 1-3 (2003): 179-83.
6. Wessells, H et al. "Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II." International journal of impotence research vol. 12 Suppl 4 (2000): S74-9.
7. Minakova E, Lang J, Medel-Matus JS, Gould GG, Reynolds A, Shin D, Mazarati A, Sankar R. "Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism." PLoS One. 2019 Jan 10;14(1):e02103389.
8. Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME. "Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study." Life Sci. 1996;58(20):1777-84.

Storage

Storage Instructions

To preserve the bioactivity of Melanotan 2, it is produced using lyophilization, which yields a stable powder. In this lyophilized state, the peptide is resistant to degradation at room temperature for several weeks. For optimal preservation, the powder should be kept in a cool, dry environment protected from light.

Reconstituted Melanotan 2 must be stored in a refrigerator (between 2 and 8 degrees Celsius). Once in solution, the peptide is more susceptible to degradation and should be used within 30 days.

Best Practices for Storing Peptides

For long-term storage, the peptide should be kept in a freezer at -20 or -80 degrees Celsius. This prevents the chemical bonds from breaking down over time. It is important to avoid freezers with an automatic defrost function, as the resulting temperature fluctuations can compromise the peptide's quality.

Preventing Oxidation and Moisture Contamination

Moisture is a significant threat to peptide stability. Always allow a frozen or refrigerated vial to reach room temperature before opening it. This ensures that no condensation forms on the product. Minimize the time the vial is open to the air to prevent oxidation.

Storing Peptides in Solution

When storing peptides in solution, it is best to divide the total amount into smaller aliquots. This allows you to thaw only what you need for a specific study, protecting the rest of the batch from unnecessary temperature changes. Using a sterile diluent like bacteriostatic water helps prevent the growth of bacteria.

Peptide Storage Containers

Peptides should be stored in high-quality glass or polypropylene vials. Glass is preferred for long-term storage because it is chemically inert and provides an excellent barrier against environmental factors. Ensure that the containers are the appropriate size to minimize the amount of air trapped inside with the peptide.