Project Number: 6202-22000-029-07-R
Project Type: Reimbursable
Start Date: Jul 1, 2009
End Date: Jun 30, 2013
The general objective of this proposed work is to develop rationally designed mimetic antagonists (and agonists) of the pyrokinin(PK)/pheromone biosynthesis activating neuropeptide (PBAN) neuropeptide (Np) class with enhanced biostability and bioavailability as prototypes for effective and environmentally friendly pest insect management agents.
This work will: 1) develop an antagonist biophore by characterizing the conformation of previously developed cyclic antagonists; 2) design and synthesize non-peptide antagonists incorporating appropriate cis/trans-Pro mimetic motifs as determined in 1; 3) develop an arsenal of topically active PK/PBAN antagonists with an array of different time-release profiles; 4) develop orally active PK/PBAN antagonists; and 5) develop both rationally designed small molecule non-peptide libraries based on the antagonist biophore determined in 1, and evaluate them in receptor binding and cloned receptor assays. The work will validate PK/PBAN receptors as pest management targets, and provide important practical information for the further design and generation of new, small, non-peptide insecticide prototypes aimed at disruption of key neuroendocrine physiological functions in pest insects.