Synthesis and diuretic activities of pseudoproline-containing analogues of the insect kinin core pentapeptide.

C-2 dimethylated/unmethylated thiazolidine-4-carboxylic acid and C-2 dimethylated oxazolidine-4-carboxylic acid were introduced into the insect kinin core pentapeptide in place of Pro(3), yielding three new analogues. NMR analysis revealed that the peptide bond of Phe(2)-pseudoproline (Psi Pro)(3) is practically 100% in cis conformation in the case of dimethylated pseudoproline-containing analogues, about 50% cis for the thiazolidine-4-carboxylic acid analogue and about 33% cis for the parent Pro(3) peptide. The diuretic activities are consistent with the population of cis conformation of the Phe(2)-Psi Pro(3)/Pro(3) peptide bonds, and the results confirm a cis Phe-Pro bond as bioactive conformation. Copyright (C) 2011 European Peptide Society and John Wiley & Sons, Ltd.