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Chemical Identity Of Bremelanotide — Worked Examples

By Editorial Desk · published 2025-09-03 · last reviewed 2025-10-26 · Info

The short version of lactam bridge fits in a sentence. The long version — which is the one that helps — is below.

This page was last updated on 2025-10-26 and is reviewed periodically as new material appears.

Chemical Identity of Bremelanotide

Across literature and commercial listings, the substance appears under several names, including bremelanotide, PT-141, and various brand designations. A CAS registry number provides a unique identifier for the compound, aiding retrieval from chemical databases. Synonym lists may also contain early development codes and descriptive chemical names. When consulting sources, researchers need to confirm that the cited names refer to the same molecular structure to avoid confusion. Naming consistency matters especially when comparing analytical data across publications.

PT-141 is a synthetic cyclic heptapeptide whose development code is bremelanotide. It belongs to the class of melanocortin receptor agonists and acts by mimicking endogenous peptide hormones. The compound originated from research on melanotan II, where investigators exploring derivatives found distinct pharmacological features. Unlike the parent compound, PT-141 showed effects on pathways related to sexual desire and function in early studies, prompting its development as a separate candidate. Its molecular design aimed to separate receptor activity from pigmentary effects.

The molecular backbone consists of seven amino acid residues joined into a ring through a disulfide bridge. This cyclic conformation is critical for receptor binding. The sequence includes an acetylated N-terminus and an amidated C-terminus, modifications that improve resistance to enzymatic breakdown. One residue is in the D-configuration, a feature that further stabilizes the peptide against protease activity. Together, the ring structure and specific stereochemistry determine selectivity among melanocortin receptor subtypes.

Receptor Pharmacology And Signalling

Whether the behavioral effect originates centrally, peripherally, or through both remains an active question. Animal experiments using receptor antagonists and site-specific injections point toward hypothalamic melanocortin circuits as a key locus, but translating those findings to humans is not straightforward. Blood pressure changes observed in trials suggest a vascular component that may be peripherally mediated. The relationship between receptor occupancy and reported effect has not been mapped in humans, and no validated biomarker predicts response. This gap makes it difficult to explain individual variability on pharmacological grounds alone.

Bremelanotide acts as an agonist at melanocortin receptors, a family of five G-protein-coupled receptors labeled MC1 through MC5. Binding studies indicate activity at several of these subtypes rather than strict selectivity for one. Signalling proceeds mainly through Gs-mediated activation of adenylyl cyclase, raising intracellular cyclic AMP. The MC4 receptor, expressed in hypothalamic and limbic circuits, is widely regarded as the subtype most relevant to sexual response. Because the molecule is not subtype-selective, effects at other melanocortin receptors are expected and are used to explain some observed side effects.

The peptide contains seven amino acids arranged in a ring, closed by a lactam bridge between a side-chain acid and an amine. This cyclic constraint holds the backbone in a defined conformation and increases resistance to enzymatic breakdown relative to linear analogs. N-terminal acetylation and a C-terminal amide further protect the molecule from exopeptidases. The result is a compound with a comparatively long circulation time for a small peptide. Structural modification of the bridge alters receptor affinity, which is one reason analogs in this family differ in their subtype preferences.

Pt-141 at a glance

PropertyValueNotes
Chemical classCyclic peptideMelanocortin receptor agonist family
Molecular weightApproximately 1025 DaFree base form
AppearanceWhite to off-white powderLyophilized product
SolubilitySoluble in waterAlso dissolves in polar organic solvents
Storage temperature-20 degrees CelsiusDry and protected from light

Analytical Characterisation and Storage Practice

The lyophilised solid is relatively stable when kept dry, protected from light and held at reduced temperature, commonly minus 20 degrees Celsius or lower for long-term storage. In solution the peptide is more vulnerable: tryptophan oxidation, hydrolysis of the lactam bridge and aggregation all become relevant over time, and the rate depends on pH, buffer composition and concentration. Repeated freeze-thaw cycles are generally avoided because they promote aggregation. Aqueous working solutions are typically prepared fresh or split into single-use aliquots to limit degradation before analysis.

Published studies differ in design, population and endpoint definition, so results are not always directly comparable across reports. Some trials used patient-reported measures of desire and distress, while others tracked physiological or behavioural outcomes. Questions that remain open include the durability of effects beyond short follow-up periods, the frequency of transient blood pressure elevation observed after administration, and whether a subtype-selective analogue could separate central effects from pigmentation-related activity. These points are usually framed as unresolved rather than settled in review literature.

Routine characterisation of bremelanotide relies on reversed-phase high-performance liquid chromatography with ultraviolet detection near 214 nm, where the peptide backbone absorbs. Mass spectrometry, typically in tandem mode with electrospray ionisation, confirms identity and supports quantification in biological matrices. Additional checks include amino acid analysis, peptide mapping after enzymatic digestion, and confirmation of the lactam bridge, since incomplete cyclisation produces a mass-shifted by-product. Purity values above 95 percent are common in reference-grade material, though reports vary in how strictly related substances are resolved from the parent peak.

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Background and Receptor Pharmacology

Bremelanotide acts as a non-selective agonist at melanocortin receptors, with reported activity at MC1R, MC3R, MC4R and MC5R. The proposed basis for its central effects is activation of MC4R populations in the hypothalamus, a region associated with appetite and reproductive signalling. Because the peptide carries a net positive charge and polar side chains, it does not cross biological membranes freely, which is one reason oral administration is not the standard route. Effects generally appear within an hour of parenteral administration and are described as centrally mediated rather than peripheral.

Bremelanotide, developed under the code PT-141, is a synthetic cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone. Its structure is Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH, with a lactam bridge joining the aspartate and lysine side chains. The molecule has the formula C50H68N14O10 and a monoisotopic mass near 1025 daltons. It is commonly prepared as the acetate salt and appears as a white to off-white lyophilised powder in solid form. The free acid is the pharmacologically relevant species, while the counter-ion improves handling and dissolution.

Peptide Handling and Storage Practice

Reverse-phase high-performance liquid chromatography is the standard method for assessing purity. Mass spectrometry confirms molecular identity and detects sequence variants or truncation products. Ultraviolet absorbance at 214 or 280 nm is used for quantification, with the choice depending on the peptide sequence. Method validation typically addresses linearity, limit of detection, and precision across a defined concentration range. Impurity profiling may also employ ion-exchange or size-exclusion chromatography, and these techniques complement one another.

Certificate of analysis documents usually report purity percentage, molecular weight, and appearance. Researchers verify identity by comparing observed and theoretical mass values. Chain-of-custody records and batch numbers help trace material from source to experiment. Independent verification of supplier claims is considered good practice when material identity is critical to a study. Records should include the storage history of each aliquot, and unexpected deviations in appearance or solubility warrant re-testing before use.

Melanocortin Receptor Agonist Pharmacology

Clinical development of bremelanotide proceeded through several reformulation attempts. An early intranasal version was discontinued, and a subcutaneous auto-injector formulation later received approval for hypoactive sexual desire disorder in premenopausal women. Approval decisions have varied by country and over time, and the product has not been universally adopted. Blood pressure elevation is a documented effect, which is why some jurisdictions require monitoring after administration. The clinical evidence base continues to evolve as additional studies are published.

Bremelanotide is a cyclic heptapeptide that acts as an agonist at melanocortin receptors. It binds MC1R, MC3R, MC4R, and MC5R, with MC4R activation considered most relevant to sexual desire pathways in the central nervous system. The molecule is a synthetic analog of alpha-melanocyte-stimulating hormone, a naturally occurring peptide involved in pigmentation and energy regulation. Early research explored its use in tanning before attention shifted toward sexual dysfunction applications. Receptor binding affinity varies across these subtypes.

Further detail

Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic that began in late 2019. The virus previously had the provisional name 2019 novel coronavirus (2019-nCoV), and has also been called human coronavirus 2019 (HCoV-19 or hCoV-19). First identified in the city of Wuhan, Hubei, China, the World Health Organization designated the outbreak a public health emergency of international concern from January 30, 2020, to May 5, 2023. SARS‑CoV‑2 is a positive-sense single-stranded RNA virus that is contagious in humans. SARS‑CoV‑2 is a virus of the species Betacoronavirus pandemicum (SARSr-CoV), as is SARS-CoV-1, the virus that caused the 2002–2004 SARS outbreak. Some animal-borne coronaviruses are more closely related to SARS-CoV-2 than SARS-CoV-1 is. The closest known relative is the BANAL-52 bat coronavirus. SARS-CoV-2 is of zoonotic origin; its close genetic similarity to bat coronaviruses suggests it emerged from such a bat-borne virus. Research is ongoing as to whether SARS‑CoV‑2 came directly from bats or indirectly through any intermediate hosts. The virus shows little genetic diversity, indicating that the spillover event introducing SARS‑CoV‑2 to humans is likely to have occurred in late 2019. Epidemiological studies estimate that in the period between December 2019 and September 2020 each infection resulted in an average of 2.4–3.4 new infections when no members of the community were immune and no preventive measures were taken.

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== Genetics == Most cases of chronic granulomatous disease are transmitted as a mutation on the X chromosome and are thus called an "X-linked trait". The affected gene on the X chromosome codes for the gp91 protein p91-PHOX (91 is the weight of the protein in kDa; the gp means glycoprotein). CGD can also be transmitted in an autosomal recessive fashion (via CYBA, NCF1, NCF2 and NCF4) which affect other PHOX proteins. The type of mutation that causes both types of CGD are varied and may be deletions, frame-shift, nonsense, and missense. A low level of NADPH, the cofactor required for superoxide synthesis, can lead to CGD. This has been reported in women who are homozygous for the genetic defect causing glucose-6-phosphate dehydrogenase deficiency (G6PD), which is characterised by reduced NADPH levels.

=== Radionuclides with half-lives of 1 day to 10 years === Ordered by half-life. The second half-life column in this table has been made unsortable, as the mixture of days and years will not sort properly. Resorting by half-life may be done no less by using the number or the half-life in seconds columns.

Sources: en.wikipedia.org

Background from the literature

While the role of rain water δD as the fundamental control on the final δD of lipids is well documented, the importance of fractionation effects from rain water to soil water and leaf water on εl/w is appreciated but remains poorly understood. Organic biomolecules are generally depleted relative to the δD of leaf water. However, differences between organisms, biosynthetic pathways, and biological roles of different molecules can lead to huge variability in fractionation; the diversity of lipid biomarkers spans a 600‰ range of δD values. Lipid biosynthesis is biochemically complex, involving multiple enzyme-dependent steps that can lead to isotope fractionations. There are three major pathways of lipid biosynthesis, known as the mevalonate pathway, the acetogenic pathway, and the 1-deoxyD-xylulose-5-phosphate/2-methylerythroyl-4-phosphate pathway. The acetogenic pathway is responsible for the production of n-alkyl lipids like leaf waxes, and is associated with a smaller δD depletion relative to source water than the other two lipid biosynthesis pathways. While leaf water is the main source of hydrogen in leaf biomolecules, relatively depleted hydrogen from acetate or NADPH is often added during biosynthesis, and contributes to the HIC of the final molecule. Secondary hydrogen exchange reactions, meaning hydrogenation and dehydrogenation reactions outside of the primary biosynthetic pathway, also contribute substantially to the variability of lipid HIC.

H2O + ATP → H+ + ADP + Pi (Mg2+ assisted, utilization of ATP for muscle contraction by ATPase) H+ + ADP + CP → ATP + Creatine (Mg2+ assisted, catalyzed by creatine kinase, ATP is used again in the above reaction for continued muscle contraction) 2 ADP → ATP + AMP (catalyzed by adenylate kinase/myokinase when CP is depleted, ATP is again used for muscle contraction) Muscle at rest: ATP + Creatine → H+ + ADP + CP (Mg2+ assisted, catalyzed by creatine kinase) ADP + Pi → ATP (during anaerobic glycolysis and oxidative phosphorylation) When the phosphagen system has been depleted of phosphocreatine (creatine phosphate), the resulting AMP produced from the adenylate kinase (myokinase) reaction is primarily regulated by the purine nucleotide cycle.

The former republics were transformed into the British colonies of the Transvaal and Orange River, and in 1910 were merged with the Natal and Cape Colonies to form the Union of South Africa, a self-governing colony within the British Empire. British expeditionary efforts were aided significantly by colonial forces from the Cape Colony, the Natal, Rhodesia, and many volunteers from the British Empire. Native African recruits contributed increasingly to the British effort. International public opinion was sympathetic to the Boers and hostile to the British. Even within the UK, there existed significant opposition to the war. As a result, the Boer cause attracted volunteers from neutral countries, including the German Empire, the United States, Russia and parts of the British Empire, such as Australia and Ireland. Some consider the war the beginning of questioning the British Empire's global dominance, due to the war's surprising duration and unforeseen losses suffered by the British. A trial for British war crimes, including the killings of civilians and prisoners of war, was opened in January 1902. The war had a lasting effect on the region and on British domestic politics.

The term flexibility is also used for well-structured proteins, but describes a different phenomenon in the context of disordered proteins. Flexibility in structured proteins is bound to an equilibrium state, while it is not so in IDPs. Many disordered proteins also reveal low complexity sequences, i.e. sequences with over-representation of a few residues. While low complexity sequences are a strong indication of disorder, the reverse is not necessarily true, that is, not all disordered proteins have low complexity sequences. Disordered proteins have a low content of predicted secondary structure. Topological approaches have been developed to search for conformational patterns in their dynamics. For instance, circuit topology has been applied to track the dynamics of disordered protein domains. By employing a topological approach, one can categorize motifs according to their topological buildup and the timescale of their formation. A common aspect of IDP structural ensembles is the ability or tendency to fold upon an interaction to a binding partner in the cell. Examples of IDP folding in a binding context are binding-coupled folding, and formation of fuzzy complexes. However, it is also possible for proteins to remain entirely disordered in a binding scenario. Conversely, it is also possible for an isolated IDP to form compact states while preserving disorder and high solvent accessibility.

Sources: en.wikipedia.org

Reference notes

In contrast, the accidental forms of S are its non-essential properties—properties that S can lose or gain without changing into a different kind of substance: the chick can lose its feathers (due to, e.g., parasites or the like) without ceasing to be an individual chicken.

Haem-using haem peroxidase and the related animal heme-dependent peroxidases DyP-type peroxidase family Catalase Manganese peroxidase some haloperoxidase Di-haem cytochrome c peroxidase Non-heme Thiol: glutathione peroxidase, peroxiredoxin vanadium bromoperoxidase Alkyl hydroperoxide reductase NADH peroxidase

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=== Material === Material selection is the most important part for designing artificial skin. It needs to be biocompatible with the body while having adequate properties for adequate function. Human skin is made of type I collagen, elastin, and glycosaminoglycan. The artificial skin by Integra is made of a copolymer composed of collagen and glycosaminoglycan. Collagen is a hydrophilic polymer whose degradation and stiffness can be controlled by the degree of cross linking. However, it can be brittle and susceptible to breakdown by the enzyme collagenase. In order to make the material tougher and more resistant, a copolymer is formed with glycosaminoglycan (GAG). GAGs are long polysaccharides that act as shock absorbers. Collagen-GAG (CG) matrices have a higher modulus of elasticity and energy needed to fracture than collagen alone, making it a more ideal material. An outer layer of silicone is normally applied to the matrix in order to serve as a protective layer. Another material that can be used in synthetic skin is elastin. Elastin has a similar effect to GAG as it reduces the tensile strength and compressive modulus of the material while increasing its toughness.

Sources: en.wikipedia.org

Frequently asked questions

What class of compound is PT-141?

It belongs to the melanocortin receptor agonist family of peptides. Its cyclic structure distinguishes it from linear peptides and shapes its receptor binding profile.

How was the compound originally identified?

It emerged from research on melanotan II. Investigators exploring derivatives observed distinct pharmacological features related to sexual function.

Which synonyms appear for PT-141?

Common names include bremelanotide and PT-141. Chemical databases may also list early development codes and descriptive names.

Is PT-141 selective for the MC4 receptor?

It is frequently described as an MC4 receptor agonist, but binding assays show activity at more than one melanocortin subtype. Selectivity is therefore relative rather than absolute. This matters when interpreting side effects tied to other receptor subtypes.

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