Melanocyte-inhibiting factor

The C-terminal tripeptide tail of oxytocin H-L-Pro-Leu-Gly-NH2 (melanocyte-stimulating hormone release inhibiting factor, MIF or melanostatin) is implicated as having a direct effect on the central nervous system. The ALeu analogue of melanostatin, [ALeu2-MIF] was prepared in view of the earlier work on the active conformation of melanostatin in which a (3-turn was implicated.11771 ALeu was prepared by the N-chlorination/dehydrochlorination reaction and then coupled with Boc-Pro-OH. 

A large number of 13C NMR studies on proline derivatives and proline peptides have appeared in the literature [815-830]. As the electron charge density of cis-proline carbons is different from that of franx-prolinc carbons, these isomers can be differentiated by nCNMR spectroscopy [826, 830]. On the basis of calculations Tonelli [831] predicted four conformations for the dipeptide Boc-Pro-Pro-OBzl, three of which could be detected by 13C NMR spectroscopy [826, 830], In proline-containing peptides the stereochemistry of the proline residue plays an important role for the conformation of these oligomers. The 13C chemical shift data of cis and trans proline derivatives, collected in Table 5.29, are useful to determine the stereochemistry of the amino acid-proline bond, e.g. in cyclo-(Pro-Gly)3, melanocyte-stimulating hormone release-inhibiting factor or thyrotropin-releasing hormone. 

Mela nocy te-stimula ting hormone (a-MSH) Ac- Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val- NH2C Unknown MSH release-inhibiting factor (MIF) most likely dopamine Regulates pigment production by melanocytes... 

The effects of melanocyte-stimulating hormone release inhibiting factor and synthetic analogs on tolerance to and physical dependence on morphine... 

Nemifitide is a peptide analogue of melanocyte-stimulating hormone release-inhibiting factor currently in clinical development for the potential treatment of moderate to severely depressed patients (93). It is rapidly absorbed, with a peak plasma concentration of 10 min and an elimination half-life of 15 to 30 minutes in most subjects. The pharmacokinetic results indicate that the dose is proportional in the dose range investigated. 

Fukuzawa T, Bagnara JT (1989) Control of Melanoblast Differentiation in Amphiba by Q-Melanocyte Stimulating Hormone, a Serum Melanization Factor, and a Melanization Inhibiting Factor. Pigment Cell Res 2 171... 

Melanocyte-stimulating-hormone release-inhibiting factor (MSH-RIF) and relea g factor (MSH-RF) 195... 

MELANOCYTE-STIMULATING-HORMONE RELEASE-INHIBITING FACTOR (MSH-RIF) AND RELEASING FACTOR (MSH-RF)... 

Melanocyte inhibitory factor (MIF) which inhibits melanocyte stimulating hormone (MSH) release. 

C. Hydroquinone inhibits the enzyme tyrosine kinase, which converts tyrosine to melanin. It also damages melanocytes. Becaplermin (A) is a recombinant human platelet-derived growth factor that is useful in enhancing wound healing. Etanercept (B) is a recombinant fusion protein approved for treatment of psoriatic arthritis and rheumatoid arthritis. Botulinum toxin (D) is a purified form of bofu-linum foxin fype A approved for fherapy of blepharospasm and sfrabismus. 

A. Hyperpigmentation is a feature of Addison disease, the diagnosis in this case. Decreased plasma cortisol because of adrenal insufficiency releases feedback inhibition of ACTH secretion by the pituitary, resulting in elevation of ACTH biosynthesis. The ACTH precursor peptide is cleaved to also yield melanocyte-stimulating hormone, the factor responsible for hyperpigmentation even in areas not exposed to sunlight. 

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