581-05-5 Usage
Description
ALPHA-MSH, also known as α-Melanocyte-stimulating hormone, is a tridecapeptide hormone secreted from the pars intermedia of the pituitary gland. It is an endogenous melanocortin receptor agonist with Ki values of 0.12, 31, 660, and 5700 nM for MC1, MC3, MC4, and MC5 receptors, respectively. ALPHA-MSH is involved in various physiological processes, including anti-inflammatory responses, regulation of food intake, and penile erections. It is synthesized and released by epidermal cells such as keratinocytes and melanocytes in response to pro-inflammatory cytokines or UV light. Poopiomelanocortin (POMC) serves as a precursor for ALPHA-MSH production.
Uses
1. Used in Anti-inflammatory Applications:
ALPHA-MSH is used as an anti-inflammatory peptide for antagonizing pro-inflammatory mediators, including TNF-α, IL-6, and NO. It also induces the production of anti-inflammatory cytokine IL-10, helping to regulate the immune response and reduce inflammation.
2. Used in Appetite Regulation:
ALPHA-MSH is used as an appetite suppressant for inhibiting food intake. This property makes it a potential therapeutic agent for treating obesity and related metabolic disorders.
3. Used in Erectile Dysfunction Treatment:
ALPHA-MSH is used as a therapeutic agent for inducing penile erections following intracerebroventricular (i.c.v.) administration, making it a potential treatment option for erectile dysfunction.
4. Used in Skin Health and Pigmentation:
As a melanocortin receptor agonist, ALPHA-MSH plays a role in skin health and pigmentation. It can be used in the development of skincare products to promote even skin tone and protect against UV-induced damage.
5. Used in Neuropeptide Research:
ALPHA-MSH, along with its agonists (NDP-MSH and MT-II) and antagonist (HS024), is used in scientific research to study the functions and interactions of melanocortin receptors (MC1R, MC3R, MC4R, and MC5R) in various physiological processes and disease states.
Synthesis and release
In rodents, α-MSH release is under strong inhibitory
control by direct innervation from hypothalamic neurons. Dopamine plays a role as a physiological melanotropin release-inhibiting hormone (MRIH). In contrast
to ACTH release from corticotropes in the pars distalis
of the pituitary, there is no apparent negative feedback
control on α-MSH release from melanotropes. Similar
mechanisms of regulation have also been demonstrated
in amphibians. In humans, the pars intermedia is functional in the fetus and neonate, whereas adults lack the
pars intermedia.
Receptors
α-MSH and other MSH peptides interact with four of
the five subtypes of melanocortin receptors (MC1R,
MC3R, MC4R, and MC5R, excluding the ACTH-specific
receptor MC2R), which are members of the GPCR family.
Among them, MC1R is a classical α-MSH receptor. ACTH
interacts with all five MC receptors.?α-MSH activates the AC/PKA pathway via
G proteins.
Clinical implications
The antiinflammatory activity of α-MSH includes
immunomodulatory effects on several resident skin cells
and antifibrogenic effects mediated via MC1R that are
expressed by dermal fibroblasts. In human mast cells,
α-MSH appears to be proinflammatory due to histamine
release. α-MSH exhibits cytoprotective activity against
ultraviolet B-induced apoptosis and DNA damage,
which is associated with the increased risk of cutaneous
melanoma in individuals with the loss of function
MC1R mutation. The congenital deficiency of POMC
results in a syndrome of hypoadrenalism, severe obesity,
and altered skin and hair pigmentation. In one case from
a Turkish family, a child who was homozygous for a
frameshift mutation in the N-terminal region of POMC,
and was thus predicted to have a loss of all POMC-derived peptides, showed typical symptoms of POMC
deficiency. However, this child did not have red hair,
unlike cases of Northern European origin.
Biological functions
α-MSH and other MSH peptides
are associated with a wide spectrum of biological functions through MC receptors that distribute in many tissues. MC1R is expressed in melanocytes, keratinocytes,
macrophages, leukocytes, and adipose tissue; MC3R is
expressed in the central nervous system (CNS), kidney,
testis, ovary, skeletal muscle, placenta, and mammary
gland; MC4R is expressed in the CNS and associated with
food intake; and MC5R is expressed in exocrine glands,
muscle, and the CNS. The representative physiological
functions of MSH peptides mediated by MC receptors
are stimulation of melanocytes in the skin to synthesize
melanin, including regulation of the eumelaninpheomelanin switch via MC1R; energy homeostasis
and natriuresis via MC3R; energy homeostasis and erectile function via MC4R; and synthesis and secretion of
exocrine gland products via MC5R.
Biochem/physiol Actions
α-Melanocyte-stimulating hormone (α-MSH) acts as an anti-inflammatory agent via down regulating the production and activity of the pro-inflammatory cytokines interleukin-1 (IL-1), tumor necrosis factor (TNF)-α and IL-6 expressed in various cells of the immune system. It also controls the nitric oxide production associated with inflammation. α?MSH inhibits nuclear factor-κB (NF-κB)-dependent gene transcription and NF-κB pathway induced by TNF and other inflammatory agents. This activity of α-MSH is mediated through the production of cyclic adenosine monophosphate (cAMP) and activation of protein kinase A (PKA) enzyme. α–MSH functions as a potent therapeutics for various conditions resulted through NF-κB activation including, inflammatory diseases, human immunodeficiency virus (HIV) replication in AIDS (acquired immunodeficiency syndrome), and septic shock. α-MSH has an essential role to play in melanin production in animals. α-MSH regulates development of several skin diseases, including cutaneous inflammation and hyper-proliferative skin diseases.
Clinical Use
The measurement of the blood concentration of MSH
has not been validated for routine clinical use. MSH analogs have recently been developed for antiobesity medication, treatment of skin diseases, and prevention of
actinic keratoses in organ transplant recipients. The
potential use of radiolabeled α-MSH peptides in melanoma imaging and the treatment of disseminated disease
has also been reported.
Purification Methods
Its solubility in H2O is 1mg/mL. It is separated from the extract by ion-exchange on carboxymethyl cellulose, desalted, evaporated and lyophilised, then chromatographed on Sephadex G-25. [Lande et al. Biochemical Preparations 13 45 1971.]
Structure and conformation
Three types of MSH molecules, with different amino
acid sequences, are contained in the common precursor
POMC in mammals. α-Melanocyte-stimulating hormone
(α-MSH) is composed of 13 aa residues. This peptide is generated from the N-terminal region of the adrenocorticotropic hormone (ACTH), and corresponds to acetylACTH(1–13)-amide. In MSH, the N-terminal Ser residue
is free, monoacetylated at the N position, or diacetylated
at the N and O positions, whereas the carboxyl terminal
is consistently in the amide form. These variations of
MSH are called desacetyl-α-MSH, α-MSH, and diacetyl-α-MSH, respectively. Of these peptides, α-MSH is a classical
α-MSH. β-MSH, which is generated from POMC via
β-lipotropin (β-LPH), is composed of 18 aa residues. Unlike
α-MSH, in β-MSH both termini are free. γ-MSH is produced
from POMC via pro-γ-MSH or N-POMC, which consists of
γ-MSH together with a joining peptide. γ-MSH (also known
as γ1-MSH) is composed of 12 aa residues in which the
N-terminus and the C-terminus are free and amide, respectively. γ3-MSH is composed of 25 aa residues in which the
N-terminal region corresponds to γ1-MSH. Each MSH segment is flanked by basic amino acid residues. Cartilaginous
fish such as sharks, rays, and ratfish possess δ-MSH in addition to the three other MSH peptides. Comparison with the
amino acid sequence and topology of POMC suggests that
δ-MSH might have evolved from β-MSH. Accordingly,
α-MSH and γ-MSH are suggested to share an antecedent.
Teleost POMC lacks γ-MSH.
Check Digit Verification of cas no
The CAS Registry Mumber 581-05-5 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,8 and 1 respectively; the second part has 2 digits, 0 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 581-05:
(5*5)+(4*8)+(3*1)+(2*0)+(1*5)=65
65 % 10 = 5
So 581-05-5 is a valid CAS Registry Number.
InChI:InChI=1/C77H109N21O19S/c1-42(2)64(65(79)106)97-75(116)61-20-13-30-98(61)76(117)54(18-10-11-28-78)88-62(103)38-85-66(107)57(34-46-36-84-50-17-9-8-16-49(46)50)94-67(108)51(19-12-29-83-77(80)81)89-70(111)55(32-44-14-6-5-7-15-44)92-72(113)58(35-47-37-82-41-86-47)95-68(109)52(25-26-63(104)105)90-69(110)53(27-31-118-4)91-74(115)60(40-100)96-71(112)56(33-45-21-23-48(102)24-22-45)93-73(114)59(39-99)87-43(3)101/h5-9,14-17,21-24,36-37,41-42,51-61,64,84,99-100,102H,10-13,18-20,25-35,38-40,78H2,1-4H3,(H2,79,106)(H,82,86)(H,85,107)(H,87,101)(H,88,103)(H,89,111)(H,90,110)(H,91,115)(H,92,113)(H,93,114)(H,94,108)(H,95,109)(H,96,112)(H,97,116)(H,104,105)(H4,80,81,83)/t51-,52-,53-,54-,55-,56-,57-,58-,59-,60-,61-,64-/m0/s1
581-05-5Relevant articles and documents
Boosting Fmoc Solid-Phase Peptide Synthesis by Ultrasonication
Merlino, Francesco,Tomassi, Stefano,Yousif, Ali M.,Messere, Anna,Marinelli, Luciana,Grieco, Paolo,Novellino, Ettore,Cosconati, Sandro,Di Maro, Salvatore
supporting information, p. 6378 - 6382 (2019/09/06)
We investigated the ultrasonication-mediated effects on the Fmoc-based solid-phase peptide synthesis (SPPS). Our study culminated with the development of an ultrasound-assisted strategy (US-SPPS) that allowed for the synthesis of different biologically active peptides (up to 44-mer), with a remarkable savings of material and reaction time. Noteworthy, ultrasonic irradiation did not exacerbate the main side reactions and improved the synthesis of peptides endowed with "difficult sequences", placing the US-SPPS among the current high-efficient peptide synthetic strategies.
Chemical synthesis and biological activity of the dogfish (Squalus acanthias) α-melanotropins I and II, and of related peptides
Eberle,Chang,Schwyzer
, p. 2360 - 2374 (2007/10/05)
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