Mimetic Analogs of Pyrokinin Neuropeptides for Pest Insect Management

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/mu l (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. (C) 2014 American Chemical Society.