The structure of bremelanotide, also known as PT-141, is a cyclic heptapeptide lactam analogue of alpha-melanocyte-stimulating hormone (α-MSH). It has the amino acid sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH.
Ac stands for acetyl, which is a capping group that protects the N-terminal amino acid from degradation. Nle stands for norleucine, which is a non-natural amino acid that is more resistant to degradation than leucine. cyclo indicates that the peptide is cyclic, meaning that the N- and C-termini are bonded together. The remaining amino acids are aspartic acid (Asp), histidine (His), D-phenylalanine (D-Phe), arginine (Arg), tryptophan (Trp), and lysine (Lys).
The cyclic structure of bremelanotide gives it a number of advantages over naturally occurring peptides. For example, it is more resistant to degradation by enzymes, which means that it has a longer half-life in the body. Additionally, the cyclic structure allows bremelanotide to bind to melanocortin receptors with higher affinity than naturally occurring peptides.
Bremelanotide structure-activity relationship (SAR)
The SAR of bremelanotide has been extensively studied, and a number of substitutions and modifications have been made to the peptide in order to improve its potency and selectivity. For example, the N-terminal amino acid, norleucine, has been shown to be essential for bremelanotide’s activity. Additionally, the D-Phe residue in position 7 of the peptide has been shown to be important for bremelanotide’s selectivity for MC3R and MC4R.
Bremelanotide structure and mechanism of action
Bremelanotide binds to melanocortin receptors in the brain and body. These receptors are involved in a variety of physiological processes, including sexual function, appetite regulation, and energy metabolism.
When bremelanotide binds to melanocortin receptors in the brain, it triggers a cascade of events that leads to increased release of dopamine and nitric oxide. Dopamine is a neurotransmitter that plays a key role in sexual desire, arousal, and pleasure. Nitric oxide is a vasodilator that increases blood flow to the genitals.
Bremelanotide also stimulates the release of other hormones that play a role in sexual function, such as testosterone and oxytocin.
The structure of bremelanotide is essential for its activity and selectivity. The cyclic structure of the peptide gives it a number of advantages, such as increased resistance to degradation and higher affinity for melanocortin receptors. The SAR of bremelanotide has been extensively studied, and a number of substitutions and modifications have been made to the peptide in order to improve its potency and selectivity.
Bremelanotide works by binding to melanocortin receptors in the brain and body, which triggers a cascade of events that leads to increased release of dopamine and nitric oxide, as well as other hormones that play a role in sexual function.
