Project Number: 6202-22320-001-02
Project Type: Reimbursable

Start Date: Dec 31, 2002
End Date: Dec 30, 2005

Objective:
Develop rationally designed neuropeptide (NP) agonist and antagonist mimetic analogs and employ them to determine the mechanisms of action and to disclose the functional diversity of the insect pyrokinin/PBAN family. Determine and enhance the bioavailability of the agonist/antagonist analogs so identified. Design and evaluate "magic bullet" and other analogs that modify the interaction characteristics with the active sites (receptors) that can either disrupt pyrokin/PBAN NP-mediated functions and/or selectively kill cells expressing the active sites (receptors) to evaluate the effect on in vivo physiological function and the viability of the NP family for the control of lepidopteran and dipteran insect pests of livestock and crops.

Approach:
Evaluate libraries of backbone cyclic NP-based analogs (BBC-NBA) in known bioassay systems associated with the pyrokin/PBAN NP family; including pheromonotropic (Lepidoptera), pupariation (Diptera), and myotropic (Blatteria and Diptera) assays to identify selective agonists and antagonists of each physiological system. Characterize the structural requirements that lead to enhanced bioactivity in each of the functions associated with pyrokinin/PBAN NP via NMR spectroscopic analysis and identify common and/or dissimilar structural features that distinguish each physiological system. Use this information to determine whether physiological functions mediated by pyrokin/PBAN NP operate through similar or dissimiliar mechanisms. Design and evaluate analogs of selective agonists/antagonists with enhanced cuticle penetrability, oral availability, and resistance to peptidase enzymes that degrade the natural NP. Evaluate the effects of selective NP mimetic agonist/antagonist analogs with enhanced bioavailability on the physiology and behavior of lepidopteran and dipteran pests of agricultural systems.

Project Team

Nachman, Ronald

Project Annual Reports

FY 2003

Related National Programs

Veterinary, Medical and Urban Entomology (104)