Location:2011 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
The goal of this 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 NPs native to target arthropod pests and their location within the nervous system. In FY 2011, significant progress was made in efforts to identify and map specific NP classes as they occur in fleahoppers and sand flies. Project work established that a specific diuretic NP plays a much larger role in herbivorous stink bugs than in the spined soldier bug, a stink bug predator. These differences can likely be exploited in the development of NP mimics that selectively disrupt water balance in the stink bug pests and not in beneficial insects that naturally prey on them. Significantly, project work established that a potent, bioavailable PK/PBAN NP agonist analog can modify two important life functions regulated by the PK/PBAN family in heliothine (Heliothis/Helicoverpa) crop pests. When administered to larvae, the analog can prevent the onset of diapause in the pupal stage. The analog can also disrupt the developmental process of ecdysis (moulting), leading to high levels of mortality. A newly developed second generation (and highly potent) analog demonstrates a selective response; it prevents the pests from entering diapause without disruption of the process of ecdysis. Diapause is a protective behavior that allows the heliothine pests to survive unfavorable environmental conditions during the winter months. These project-developed analogs will serve as leads for novel control agents that operate via manipulation of diapause in pest insects. Accomplishments to date by this project 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.