Title: Mimetic analogs of pyrokinin neuropeptides for pest management Author
Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: June 20, 2014
Publication Date: October 28, 2014
Citation: Nachman, R.J. 2014. Mimetic analogs of pyrokinin neuropeptides for pest management. In: Gross, A., Coats, J.R., Duke, S.O., Seiber, J.N., editors. Biopesticides: State of the Art and Future Opportunities. Washington, DC: American Chemical Society. p. 83-94. Interpretive Summary: Insect pests have developed resistance to several conventional pesticides, and new approaches are needed for pest management. Although neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions, the neuropeptides hold little promise as pest control agents because they can be degraded in the target pest. New, selective control agents may be developed by designing mimics of these neuropeptides that resist degradation and either inhibit or over-stimulate critical neuropeptide-regulated life functions. This book chapter reviews the development of neuropeptide mimics that induce oral aphicidal effects that match or exceed the potency of some commercially available insecticides, and that work via a novel and selective mode of action. Other neuropeptide mimics can prevent the onset of the protective state of diapause in the corn earworm, inducing the crop pest to commit a form of ‘ecological suicide’. Alternatively, still other mimics can block the activity of the native hormone. These results provide the basis for the development of practical neuropeptide-like substances that can effectively control pest insects in an environmentally friendly fashion.
Technical Abstract: Neuropeptides are potent regulators of critical life processes in insects, but are subjected to rapid degradation by peptidases in the hemolymph (blood), tissues and gut. This limitation can be overcome via replacement of peptidase susceptible portions of the insect neuropeptides to create analogs with enhanced biostability. The pyrokinins stimulate gut motility and regulate other functions in certain insects, but unmodified members demonstrate little or no effect when fed to pea aphids (Acyrthosiphon pisum). However, biostable analogs demonstrate potent oral antifeedant and aphicidal effects. The most active of the biostable analogs shows an LC50 value of 0.042 nmole/µl (LT50 = 1.0 days), approaching the potency of some commercial aphicides. The aphicidal activity of a biostable pyrokinin can be blocked with an antagonist, indicating the mechanism occurs via a neuropeptide receptor and represents a novel and selective mode of action. Biostable agonists of diapause hormone (a pyrokinin) can prevent the onset of the protective state of diapause in the corn earworm, inducing the crop pest to commit a form of ‘ecological suicide’. Alternatively, an antagonist can block the activity of the native hormone. Biostable neuropeptide analogs represent important leads in the development of alternate, environmentally sound pest insect control agents.