Biostable analogs of insect kinin and insectatachykinin neuropeptides: A review of novel classes of antifeedants and aphicides

Neuropeptides are regulators of critical life processes in insects, but are subject 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 with non-natural residues or moieties to create analogs with enhanced biostability. Two neuropeptide families, the insect kinins and insectatachykinins, stimulate gut motility and Malpighian tubule fluid secretion in certain insects but unmodified members demonstrate little or no effect when fed to pea aphids (Acyrthosiphon pisum) in an artificial diet. Nonetheless, biostable analogs developed via the strategic introduction of either bulky Aib residues and/or β-amino acids demonstrate potent antifeedant and aphicidal effects when administered orally; whereas other biostable analogs are inactive. Although the precise mechanism of action has not been delineated, the activity may be associated with disruption of the physiological processes that these neuropeptides regulate in insects. The most active of the biostable insect kinin and insectatachykinin analogs show LC50 values of 0.063 nmole/μl (LT50 = 1.68 days) and 0.0085 nmole/μl (LT50 = 1.1 days), respectively; matching or exceeding the potency of some commercially available aphicides. The biostable analogs represent important leads in the development of alternative, environmentally sound aphid control agents.