Iodination associated inactivation of β-melanocyte stimulating hormone

Contrary to other published reports, iodinated β-melanocyte stimulating hormone (β-MSH) is without biological activity as measured by frog skin bioassay, melanoma (mouse S-91) adenylate cyclase assay, or melanoma tyrosinase assay. Inactivation results in part from oxidation of the methionine residue by the chloramine T and sodium metabisulfite used in the iodination reaction. Replacement of the methionine of β-MSH with norleucine by solid phase synthesis results in an analogue which is more resistant, but not completely resistant, to inactivation. Thus, in order to obtain a biologically active radioligand for radioreceptor studies, further tailoring of the hormone and/or modification of the iodination procedure will be needed.