Stereochemistry of insect kinin tetrazole analogues and their diuretic activity in crickets.
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.
Nachman
Ronald J
RJ
US Department of Agriculture, Areawide Pest Management Research Unit, Southern Plains Agricultural Research Center, ARS, College Station, TX 77845, USA. nachman@tamu.edu
Coast
Geoffrey M
GM
Kaczmarek
Krzysztof
K
Williams
Howard J
HJ
Zabrocki
Janusz
J
D000595:Amino Acid Sequence; D000818:Animals; D004064:Digestive System / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects*; D006135:Gryllidae / Q000187:drug effects / Q000502:physiology*; D007301:Insect Hormones / Q000737:chemistry* / Q000494:pharmacology; D007306:Insecticides / Q000138:chemical synthesis / Q000494:pharmacology; D007705:Kinins / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D012996:Solutions; D013777:Tetrazoles / Q000494:pharmacology*
D007301:Insect Hormones; D007306:Insecticides; D007705:Kinins; D009842:Oligopeptides; D012996:Solutions; D013777:Tetrazoles; C045574:1H-tetrazole