A re-examination of the conformation of secretin in water

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 N-terminus, while newly accumulated evidence points to the C-terminal area. The possible role of ion pairs 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 carboxyl groups 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 significant decrease in helical character. This loss of "structure" is even more pronounced in the 9-glutamine-15-asparagine tricosapeptide. Thus, ion-pair formation is indeed implicated as one of the forces which stabilize the folded conformation of the chain. Possible correlations between biological activity and secretin-like architecture were studied on several smooth muscle preparations.