Stereochemistry of insect kinin tetrazole analogues and their diuretic activity in crickets.

Abstract

Insect kinin analogues of the sequence Phe-Phe-psi[CN(4)]-Ala-Trp-Gly-NH(2) containing (L-Phe(2),L-Ala(3)) and (L-Phe(2),D-Ala(3)) stereochemical variants of the tetrazole moiety, a mimic of the type VI beta-turn, demonstrate significant agonist and partial antagonist activity, respectively, in a cricket diuretic bioassay. A comparison of the solution conformations of these two stereochemical variants indicates a structural basis for their divergent bioactivities. The (D-Phe(2),D-Ala(3)) stereochemical variant was synthesized and found to demonstrate significant agonist activity. The results further define stereochemical requirements for the diuretic activity of insect kinins in crickets and provide valuable information for the design of biostable analogues capable of disrupting digestive and diuretic processes in pest insects.