Sodium hydroxide treatment of l-histidyl- l-phenylalanyl- l-arginyl- l-tryptophylglycine and its potentiated melanocyte-stimulating activity in vitro

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Treatment of l-histidyl- l-phenylalanyl- l-arginyl- l-tryptophylglycine, a common fragment of α- and β-MSH and ACTH, with 0.1 N sodium hydroxide at 100° for 10 min brought about a 40-fold increase in the MSH activity on frog-skin melanocytes in vitro. Chemical and enzymatic examinations of this treated peptide showed that one quarter of the arginine was converted to ornithine and four amino acid residues: histidine, phenylalanine, arginine and tryptophan, were racemized. As far as the MSH activity in vitro is concerned, potentiation is the only phenomenon which was observed. Neither retarded nor prolonged effects of its action could be detected in this product. When the relative potencies of the synthetic stereoisomers of the pentapeptide were measured against the darkening value produced by a constant amount of the all- l pentapeptide, l-histidyl- d-phenyalanyl- l-arginyl- l-tryptophylglycine and l-histidyl- l-phenylalanyl- l-arginyl- d-tryptophylglycine exhibited some 160 and 20 times higher activity than that of the all- l pentapeptide respectively. Based on these observations, the relationship between structure and the potentiated activity of the alkali-treated all- l pentapeptide is discussed. A possible explanation for the phenomenon of appearance or disappearance of the potentiated activity in alkali-treated ACTH and MSH's is proposed.