A New Synthesis of the Pentapeptide L-Histidyl-L-Phenylalanyl-L-Arginyl-L-Tryptophyl-Glycine and its Melanocytestimulating Activity

Abstract

A SYNTHESIS of the pentapeptide H.His-Phe-Arg-Try-Gly.OH along classical lines has recently been described by Hofmann et al. ¹. The amino-acid sequence of this peptide, which occurs in adrenocorticotropic (ACTH) and melanocyte-stimulating (MSH) hormones², presents a number of considerable difficulties for chemical synthesis, chiefly owing to the presence of tryptophan, arginine and histidine. In this communication, we wish to report the synthesis of this pentapeptide in a stepwise manner beginning at the C-terminus with the p-(p′-methoxy-phenylazo)-benzyloxy carbonyl group (MZ group), described by one of us³, used as the amino-protecting agent. In addition, the p-toluenesulphonyl (tosyl) group was introduced to protect the guanidino group of arginine, since this protecting group resists catalytic hydrogenation and is easily removed by sodium in liquid ammonia. When the peptide was assayed either in the hypophysectomized frog or on frog skin in vitro, it was found to possess melanocyte-stimulating activity.