Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have prepared several alpha-melanotropin (alpha-MSH) analogues with tyrosine substituted for methionine at the 4-position and determined their melanotropic activities on the frog (Rana pipiens), lizard (Anolis carolinensis) and S-91 (Cloudman) mouse melanoma adenylate cyclase bioassays. The potencies of Ac-[Tyr4]-alpha-MSH4-10-NH2 and Ac-[Tyr4]-alpha-MSH4-11-NH2 were compared with alpha-MSH and with their corresponding methionine and norleucine substituted analogues. The Tyr-4 analogues were found to be less active than the Nle-4 analogues on both the frog and lizard assays. Ac-[Tyr4]-alpha-MSH4-10-NH2 was found to be less active than Ac-[Tyr4]-alpha-MSH4-11-NH2 on the lizard bioassay, but more active than the longer fragment on the frog skin assay. Ac-[Tyr4]-alpha-MSH4-10-NH2 exhibited extremely prolonged biological activity on frog skin, but not on lizard skin, while the melanotropic activity of Ac-[Tyr4]-alpha-MSH4-11-NH2 was rapidly reversed on both assay systems. The increased potency of Ac-[Tyr4]-alpha-MSH4-10-NH2 over Ac-[Tyr4]-alpha-MSH4-11-NH2 on frog melanocytes may be related to the fact that the shorter 4-10 analogue exhibits prolonged biological activity. Interestingly, it was found that both Tyr-4 analogues were partial agonists on the mouse melanoma adenylate cyclase bioassay, and stimulated the enzyme to only about 50% of the maximal activity of alpha-MSH. We reported previously that replacement of L-Phe-7 by its D-enantiomer in [Nle4]-alpha-MSH and its Nle-4 containing analogues resulted in peptides with increased potency and in some instances prolonged activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative biological activities of potent active-site analogues of alpha-melanotropin. Effect of tyrosine substitution at position-4. 633 85

In previous work we reported that [Cys4,Cys10]-alpha-MSH (II) and Ac-[Cys4,Cys10]-alpha-MSH4-13-NH2 (III) were superpotent melanotropins. Ac-[Cys4,Cys10]-alpha-MSH4-10-NH2 (VI), which constitutes the cyclic analogue of the putative active site sequence -Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10- of alpha-MSH, was much less active. In the present investigation the contribution of the Lys11 and Pro12 residues of the C-terminal carboxamide tripeptide -Lys11-Pro12-Val13-NH2 to the potency of Cys4,Cys10 containing cyclic melanotropins was studied. Ac-[Cys4,Cys10]-alpha-MSH4-11-NH2 (V) was less potent than alpha-MSH in the frog and lizard skin bioassays and the mouse S-91 (Cloudman) melanoma adenylate cyclase assay but more potent than Ac-[Cys4,Cys10]-alpha-MSH4-10-NH2 in the three assays studied. Ac-[Cys4,Cys10]-alpha-MSH4-12-NH2 (IV) was considerably more potent than the cyclic 4-11 melanotropin and was, in fact, equipotent or even slightly more potent than [Cys4,Cys10]-alpha-MSH and Ac-[Cys4,Cys10]-alpha-MSH4-13-NH2 over the linear portion of the dose-response in all three bioassays. These results demonstrate that Lys11 and Pro12 but to a lesser extent Val13 of the C-terminal tripeptide sequence contributes to the potency of the cyclic melanotropins. The further substitution of a D-Phe7 for the L-Phe7 residue into the cyclic 4-12 analogue resulted in a highly potent compound Ac-[Cys4,D-Phe7,Cys10]-alpha-MSH4-12-NH2 (VII) that exhibited highly prolonged biological activity.
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PMID:Cyclic melanotropins. 5. Importance of the C-terminal tripeptide (Lys-Pro-Val). 633 95

Biocytin derivatives of a superpotent analogue of alpha-melanotropin, [Nle4,D-Phe7]-alpha-MSH, were prepared. [N alpha-Bct-Ser1, Nle4,D-Phe7]-alpha-MSH and [12-Bct-N alpha-dodecanoyl-Ser1,Nle4,D-Phe 7]- alpha-MSH were synthesized by solid-phase techniques, and the coupling of biotin and 12-aminododecanoic acid was achieved through their succinimido esters. These melanotropins possessed almost identical actions to [Nle4,D-Phe 7]- alpha-MSH as determined by several melanocyte bioassays. Both biocytin derivatives were highly potent agonists and exhibited prolonged biological activity as determined in the frog and lizard skin bioassays. Both biotinylated peptides were at least equipotent to alpha-MSH in stimulating Cloudman S91 mouse melanoma tyrosinase activity. The analogues were resistant to inactivation by alpha-chymotrypsin.
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PMID:Synthesis and biological actions of highly potent and prolonged acting biotin-labeled melanotropins. 643 88

We have studied the behaviour of 125I-labelled alpha-MSH under different experimental conditions. Until now, the chloramine T method had been used by most investigators with variable results. We have tested three other labelling techniques based on 125I mild oxidation: (1) an enzymatic method with lactoperoxidase, (2) a sparingly soluble chloramine method (T.D.G.U.) and (3) modified chloramine T procedure, 'the iodine volatilization method'. Labelled hormone obtained after each kind of iodination was assayed for immunoreactivity. In addition, time course degradation was measured by classical RIA incubation procedures. Charcoal-dextran was used to separate bound and free antigen. We have found chloramine T-iodinated alpha-MSH to be significantly more damaged than preparations obtained by other methods and to be less stable when stored at -18 degrees C. No differences were found between the differently labelled 125I-labelled alpha-MSH fresh preparations in binding to surface receptors of human melanoma cell lines in culture.
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PMID:Comparison and evaluation of different methods for alpha-MSH labelling. 675 23

A reproducible and sensitive assay for melanotropic agents is described employing mouse melanoma cells in culture and measuring tyrosinase activity in terms of production of tritiated water from L-(ring-3,5-3H)-tyrosine. Molar concentrations of peptides inducing one-half maximal stimulation of tyrosinase activity were: beta-MSH, 1 +/- 2 x 10(-9); alpha-MSH and Beta h-LPH, 1 +/- 2 x 10(-8); ACTHp, 1 +/- 2 x 10(-7). Beta p 9-18-MSH and melanotropin potentiating factor, beta s 88-91-LPH exhibited no activity at concentrations as high as 10(-5)M.
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PMID:Assay of melanotropic peptides in an in vitro mammalian system. 679 95

On 40 healthy male volunteers with different pigmentation level (Caucasians: skin types I-III, negroes: skin type VI) the basal alpha-MSH-secretion as well as the influence of UV-A-wholebody-irradiation (6 J/cm2) on alpha-MSH-serum concentration were measured. The mean basic values of red-haired and blondes are with 73,0 respectively 71,6 pg/ml significantly lower than the mean values of negroes with 99,6 pg/ml. After UV-A-irradiation the alpha-MSH mean values within one hour among red-haired persons increase 26,7%, among blondes increase 22,6%. Dark-haired caucasians (skin type III) as well as negroes show no significant changes in alpha-MSH serum level. These results support a peripheral sensor for UV-A-rays which induce a hypothalamic-pituitary response (alpha-MSH secretion) obviously on a nervous way. One can point out that genetic and/or racial characteristics influence this central-nervous reaction due to UV-A-irradiation of the skin. The connection between the development of malignant melanoma and the UV-A-induced changes of alpha-MSH level is discussed.
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PMID:[Modification of alpha-MSH by UVA irradiation of the skin]. 687 38

The synthesis and purification of several analogues of the melanotropins with amino acid substitutions at the tyrosine-2 and methionine-4(7) positions are reported. The compounds synthesized included [4-norleucine]-alpha-MSH, [7-norleucine]-beta p-MSH, [2-3',5'-diiodotyrosine]-alpha-MSH, [2-D-tyrosine]-alpha-MSH, and [2-phenylalanine,4-norleucine]-alpha-MSH. The biological activities of these derivatives were measured and compared on normal melanocytes (frog skins) and on transformed melanocytes (mouse melanoma adenylate cyclase), over the entire dose-response range. All compounds tested were full agonists in both assay systems but varied considerably in potency. The relative potencies in the frog skin assay (alpha-MSH = 1.0) were as follows: [Nle7]-beta p-MSH (5.2) > [Nle4]-alpha-MSH (2.3) > alpha-MSH (1.0) > [Phe2,Nle4]-alpha-MSH (0.80) > beta p-MSH (0.55) > [I2-Tyr2]-alpha-MSH (0.12) > [D-Tyr2]-alpha-MSH (0.04). The relative potencies in the melanoma adenylate cyclase system were [Nle7]-beta p-MSH (4.2) > beta p-MSH (2.2) > [Nle4]-alpha-MSH (2.0) > alpha-MSH (1.0) approximately equal to [Phe2,Nle4]-alpha-MSH (0.9) > [I2-Tyr2]-alpha-MSH (0.40) > [D-Tyr2]-alpha-MSH (0.20). There appears to be some differences in structural specificity at the melanotropin receptors of the two cell systems.
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PMID:Synthesis and structure-function studies of melanocyte stimulating hormone analogues modified in the 2 and 4(7) positions: comparison of activities on frog skin melanophores and melanoma adenylate cyclase. 745 98

Microvascular endothelial cells were isolated from the brains of C57 mice and cultured in selective growth media. The isolation and culture techniques employed in this study minimised the contamination by nonendothelial cells such as astrocytes, pericytes, and smooth muscle cells. Microvascular endothelial cells examined using phase contrast light microscopy grew as small colonies of spindle-shaped cells which merged together to form typical contact-inhibited monolayers. The endothelial origin of these cells was determined using several established characterisation techniques. Preliminary receptor binding studies at 4 degrees using [125I-Tyr2, Nle4, D-Phe7]alpha-melanocyte-stimulating hormone ([125I-Tyr2, Nle4, D-Phe7]alpha-MSH) suggested the possibility that melanocortin receptors were present on the surface of brain microvascular endothelial cells. Subsequent binding isotherms confirmed that a small population of high-affinity melanocortin receptors was expressed. The existence of a specific binding site for alpha-MSH was confirmed by photoaffinity labeling with the 4-(1-azi-2,2,2,-trifluoroethyl)benzoic acid (ATB) derivative, [125I-Tyr2, Nle4, D-Phe7, (ATB)-Lys11] alpha-MSH. SDS-PAGE analysis identified the presence of a specific band with a molecular mass of approximately 45 kDa, which was consistent with previous data on melanoma melanocortin receptors, and represented a ligand-receptor complex. This study suggests that a receptor for alpha-MSH is expressed on the extracellular surface of murine brain microvascular endothelial cells; however, the physiological role of this receptor is as yet unknown.
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PMID:Identification of a melanocortin receptor expressed by murine brain microvascular endothelial cells in culture. 747 77

alpha-Melanocyte-stimulating hormone (alpha-MSH1-13), a peptide derived from proopiomelanocortin, has remarkable anti-inflammatory and antipyretic activities. This peptide and a tripeptide that forms the COOH-terminal portion of the molecule (alpha-MSH11-13; Lys Pro Val) inhibit inflammation when given centrally or peripherally. Because of the similarity in their actions, the tripeptide has been presumed to be the amino acid message sequence underlying the effects of alpha-MSH1-13. To test the possibility that the two peptides occupy the same receptors, competitive binding experiments were performed with B16 mouse melanoma cells that are known to have alpha-MSH1-13 receptors. In these experiments, alpha-MSH11-13 did not inhibit binding of a radiolabelled alpha-MSH1-13 analog. This finding suggests that alpha-MSH1-13 and alpha-MSH11-13 exert their anti-inflammatory/antipyretic/anticytokine effects via stimulation of separate receptors. Because alpha-MSH inhibits the effects of several cytokines including inflammation caused by interleukin (IL)-6 and IL-8, the capacity of these cytokines to compete for alpha-MSH binding sites was tested. There was no evidence that these proinflammatory cytokines bind to alpha-MSH receptors on murine melanoma cells. Although further tests with host cells involved in inflammation are required, the latter result is the first evidence that the mechanism of anticytokine action of alpha-MSH does not depend upon peptide/cytokine competition for binding sites.
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PMID:Binding of anti-inflammatory alpha-melanocyte-stimulating-hormone peptides and proinflammatory cytokines to receptors on melanoma cells. 748 22

alpha-Melanocyte-stimulating hormone (alpha-MSH) is implicated in pigmentation, central nervous system and immune system functions, growth, mitogenesis, and melanoma. Evaluation of these roles has been hindered by the lack of alpha-MSH antagonists. A combinatorial chemistry-based diffusion assay is used to find random tripeptides that antagonize normal frog and human melanoma MSH receptors and to identify pharmacological groups responsible for receptor interaction. The alpha-MSH antagonist D-Trp-Arg-Leu-NH2 is used to demonstrate directly the contribution of MSH to normal skin tone in frogs following injection or topical application.
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PMID:Combinatorial diffusion assay used to identify topically active melanocyte-stimulating hormone receptor antagonists. 770 44


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