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2010 Annual Report

1a. Objectives (from AD-416)
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.

1b. Approach (from AD-416)
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.

3. Progress Report
This is a new project, funded by a BARD grant, being conducted cooperatively with an Israeli scientist. The goal of the project is to develop and exploit insect neuropeptide (NP) technology to develop more effective and environmentally friendly methods for pest arthropod control. The development of NP-based insect control technology requires an understanding of the specific structures of insect neuropeptides native to target arthropod pests and their location within different body organs and tissues. In FY 2010, neuropeptides of a class that regulate muscular and water balance activities were studied in a variety of insects. Mapping of where these hormones reside in the deer tick (Ixodes scapularis, which transmits Lyme disease) and in the yellow fever mosquito (Aedes aegypti) was accomplished. Detailed information was gained on a water balance neuropeptide that occurs in the assassin bug (Rhodnius prolixus, which transmits Chagas disease); the results of this work are being published in the Proceedings of the National Academy of Sciences. Additional work focused on neuropeptides in the southern green stink bug (Nezara viridula) and the green stink bug (Acrosternum hilare); the work established that certain NP are active in water balance regulation in these insects; four published or accepted manuscripts have thus far arisen from the stink bug work. Work focused on insects of the genus Heliothis, which are important crop pests, has established parameters for exploiting the cuticle (outside skin) of the living insects to serve as a reservoir for absorption and subsequent sustained release of toxic NP mimics. Accomplishments under this project to date have significantly added to the scientific foundation necessary for ultimate development of effective and practical neuropeptide-based insect control agents that will act within living insects to disrupt critical life processes and with minimal or no adverse environmental effects.

4. Accomplishments