A RE‐EXAMINATION OF THE CONFORMATION OF SECRETIN IN WATER

Abstract

SUMMARY An examination of a series of peptides corresponding to partial sequences of secretin and the application of empirical conformational parameters to the sequence has reopened the question about the position of the short helical stretch in the folded chain. In earlier studies, this was tentatively placed near the Nterminus, while newly accumulated evidence points to the C‐terminal area. The possible role of ion paris in the stabilization of the folding was investigated by the preparation and examination of synthetic analogues of the C‐terminal tricosapeptide part of secretin. The carboxy grups of glutamic acid (in position 9) and of aspartic acid (in position 15) were replaced by carboxamides. The 9‐glutamine and the 15‐asparagine analogues show a signifcant decrease in helical character. This loss of 'structure’is even more pronounced in the 9‐glutamine‐15‐asparagine tricospetide. Thus, ion ‐pair formation is indeed implicated as one of the forces which stabilize the folded conformation of the chain. Possible corelations between biological activity and secretin‐like architecture were studied on severl smooth muscle preparations.