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United States Department of Agriculture

Agricultural Research Service

Title: Stereochemistry of Insect Kinin Tetrazole Analogues and Diuretic Activity in Crickets

Authors
item Nachman, Ronald
item Coast, Geoffrey - UNIV OF LONDON
item Kaczmarek, Krysztof - TECH UNIV, LODZ, POLAND
item Williams, Howard - TEXAS A&M UNIV
item Zabrocki, Janusz - TECH UNIV, LODZ, POLAND

Submitted to: Acta Biochimica Polonica
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 3, 2004
Publication Date: March 31, 2004
Citation: Nachman, R.J., Coast, G.M., Kaczmarek, K., Williams, H.J., Zabrocki, J. 2004. Stereochemistry of insect kinin tetrazole analogues and diuretic activity in crickets. Acta Biochimica Polonica. 51(1):121-127.

Interpretive Summary: Neuropeptides are short chains of amino acids (the building blocks of proteins) that regulate aspects of reproduction, development, water balance and digestion that are critical for insect survival. Nevertheless, these insect peptides in and of themselves hold little promise as insect control agents because of susceptibility to being degraded in the target insect, and inability to pass through the outside skin (cuticle) and/or digestive tract of the insect. We must design neuropeptide mimics that resist degradation by enzymes in the digestive tract and blood of pest insects and interact with the active site within the pest insect in such a way as to either over-activate or block critical, neuropeptide-regulated life functions. This work describes neuropeptide mimics that incorporate a component that protects the parent neuropeptide from enzyme inactivation while at the same time providing data that defines the specific shapes required to either activate or block the active site. This information is invaluable in the design of biostable mimics capable of disrupting digestive and diuretic processes in insects. The work brings us a step closer to the development of practical neuropeptide-like substances that will be effective in controlling pest insects in an environmentally friendly fashion.

Technical Abstract: Insect kinin analogues of the sequence Phe-Phe-psi[CN4]-Ala-Trp-Gly-NH2 containing (L-Phe2,L-Ala3) and (L-Phe2,D-Ala3) 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-Phe2,D-Ala3) 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.

Last Modified: 11/28/2014
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