Effects of Chloramine T and lodination on the Biological Activity of Melanotropin

Abstract
.alpha.-Melanotropin was iodinated using chloramine T and NaI, which was associated with a complete loss of the biological activity of the hormone. Amino acid analyses showed that the tyrosine, methionine, tryptophan and histidine residues were all modified in the iodination reaction. If one exposes .alpha.-melanotropin or .beta.-melanotropin to iodination conditions, but in the absence of NaI, a complete loss of biological activity is observed at relatively low concentrations of the reagent. The biologically active structural analogs [4-Nleu].alpha.-melanotropin and [7-Nleu].beta.-melanotropin are only significantly inactivated if NaI is also present in the reaction mixture. The potency of [2-diiodotyrosine].alpha.-melanotropin was markedly less than that of the unsubstituted hormone. However, the observed biological activity of this compound was not sufficiently low to account for the loss of activity resulting from oxidative (chloramine T-induced) iodination. [2-Phen,4-Nleu].alpha.-melanotropin also biologically active and resistant to the oxidation by chloramine T, suffered loss of biological activity upon treatment with chloramine T and I-. Amino acid analyses showed that the tryptophan and histidine residues were chemically modified in this case. Iodination of .alpha.-melanotropin using chloramine T can result in at least 4 changes in the molecule: oxidation of the methionine residue; incorporation of I into the tyrosine residue; modification of histidine and modification of tryptophan.

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