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.
Similar content being viewed by others
References
Hofmann, K., Woolner, M. E., Spuhler, G., and Schwartz, E. T., J. Amer. Chem. Soc., 80, 1486 (1958).
Li, C. H., “Adv. Prot. Chem.”, 11, 101 (1956); 12, 269 (1957).
Schwyzer, R., Sieber, P., and Zatsko, K., Helv. Chim. Acta, 41, 491 (1958).
Schwyzer, R., Feurer, M., Iselin, B., and Kagi, H., Helv. Chim. Acta, 38, 80 (1955); the carbobenzoxy group is designated the Z group.
Sheehan, J. C., and Hess, G. P., J. Amer. Chem. Soc., 77, 1067 (1955).
Levy, A. L., Nature, 174, 126 (1954).
Goodwin, T. W., and Morton, R. A., Biochem. J., 40, 628 (1946).
Shizume, K., Lerner, A. B., and Fitzpatrick, T. B., Endocrinol., 54, 553 (1954).
Hofmann, K., Thompson, T. A., and Schwartz, E. T., J. Amer. Chem. Soc., 79, 6087 (1957).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
SCHWYZER, R., LI, C. A New Synthesis of the Pentapeptide L-Histidyl-L-Phenylalanyl-L-Arginyl-L-Tryptophyl-Glycine and its Melanocytestimulating Activity. Nature 182, 1669–1670 (1958). https://doi.org/10.1038/1821669a0
Issue Date:
DOI: https://doi.org/10.1038/1821669a0
- Springer Nature Limited
This article is cited by
-
An HPLC system for use in the development of new arginine protecting groups
Chromatographia (1990)
-
Protease-catalyzed synthesis of melanocyte-stimulating hormone (MSH) fragments
Journal of Protein Chemistry (1983)
-
Melanophoren-stimulierende Wirksamkeit von Aminos�uren
Die Naturwissenschaften (1967)
-
Chemische Synthese der Melanotropine und des corticotropen Hormons der Hypophyse
Die Naturwissenschaften (1966)