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Chemical Synthesis and Biological Activity of the Dogfish (Squalus acanthias) α‐melanotropins I and II, and of related peptides
Author(s) -
Eberle Alex,
Chang YaoShih,
Schwyzer Robert
Publication year - 1978
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19780610709
Subject(s) - methionine , chemistry , tripeptide , squalus acanthias , valine , amino acid , stereochemistry , in vitro , methionine sulfoxide , biochemistry
The purpose of this investigation is to provide synthetic proof for the structure of dogfish ( Squalus acanthias ) α‐MSH and to investigate the consequences of the presence of methionine in position 13 and the lack of the N ‐terminal acetyl group in this hormone. Because of the facile oxidation of methionine (13) during handling or storage, a number of specifically oxidized hormones (Met 4 and Met 13 ) as well as tripeptides belonging to the C ‐terminal second message sequence were investigated. All the products were prepared by classical methods in homogeneous solution; intermediate and end products were extensively purified and characterized ( Tables 3 and 4 ). The assays for melanotropic activity were performed in vitro with the modified reflectometric assay using the skin of Rana pipiens . It is concluded that the structures assigned to dogfish α‐MSH I and II are correct and that the isolated samples contain slight quantities of [13‐methionine ( S ‐oxide)]dogfish α‐MSH and [4, 13‐bis‐methionine ( S ‐oxide)]dogfish α‐MSH. The peptides with methionine in position 13 are as active in this assay as those containing valine. This also holds for the NH 2 /OH interchange distinguishing dogfish α‐MSH I from dogfish α‐MSH II. However, the lack of the N ‐terminal acetyl group strongly reduces the biological activity. Its introduction into dogfish α‐MSH I results in a product that is equipotent with mammalian α‐MSH. These and other conclusions are discussed in detail.