Title: Biostable analogs of insect kinin and insectatachykinin neuropeptides: Novel antifeedants and aphicides Authors
Submitted to: Pestycydy/Pesticides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 26, 2012
Publication Date: June 15, 2012
Citation: Nachman, R.J., Smagghe, G. 2012. Biostable analogs of insect kinin and insectatachykinin neuropeptides: Novel antifeedants and aphicides. Pestycydy/Pesticides. 1-4:23-24. 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. We report on the development of versions of two classes of neuropeptides with enhanced resistance to degradation and that demonstrate potent aphicidal activity when fed to the pea aphid. Some of the synthetic versions match or exceed the potency of some aphicides that are used commercially. The pea aphid causes hundreds of millions of dollars of crop damage every year, and many populations have already acquired resistance towards multiple conventional and modern insecticides, making a search for alternative strategies urgent. The results suggest potential for using such agents or next-generation derivatives for pest management.
Technical Abstract: Neuropeptides are potent 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 beta-amino acids demonstrate potent antifeedant and aphicidal effects when administered orally. 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/ul (LT50 = 1.68 days) and 0.0085 nmole/ul (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 alternate, environmentally sound aphid control agents.