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 (ΨPro) 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 ‐ΨPro 3 /Pro 3 peptide bonds, and the results confirm a cis Phe‐Pro bond as bioactive conformation. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.