|SMAGGHE, GUY - Ghent University
|MAHDIAN, KAMRAN - Ghent University
|ZUBRZAK, PAWEL - Pepceuticals Limited
Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/2/2009
Publication Date: 3/10/2010
Citation: Smagghe, G., Mahdian, K., Zubrzak, P., Nachman, R.J. 2010. Antifeedant activity and high mortality in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae) induced by biostable insect kinin analogs. Peptides. 31:498-505.
Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling insect pests. The basic premise of this research is that neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions. Nevertheless, neuropeptides in and of themselves hold little promise as pest control agents because of susceptibility to being degraded in the target pest. New, selective control measures may be developed by designing metabolically stable mimics of these neuropeptides that interact with the active site within the agricultural pest in such a way as to either inhibit or over-stimulate critical neuropeptide-regulated life functions. Neuropeptides of the insect kinin class regulate such critical processes as water balance, digestion and satiety in a variety of insects. We report that biostable versions of insect kinin neuropeptides demonstrate anti-feedant activity and high mortality when fed to aphids, important agricultural pests. One of the neuropeptide versions has been shown to match or exceed the potency of some commercial aphicides. These potent, biostable versions represent genuine leads for novel agents that can kill aphid pests. The work brings us a major step closer to the development of practical neuropeptide-like substances that will be effective in controlling pest aphids in an environmentally friendly fashion.
Technical Abstract: The insect kinins are multifunctional neuropeptides found in a variety of arthropod species, including the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae). A series of biostable insect kinin analogs based on the shared C-terminal pentapeptide core region were fed in solutions of artificial diet to the pea aphid over a period of three days and evaluated for antifeedant and aphicidal activity. The analogs contained either alpha,alpha-disubstituted or beta-amino acids in key positions to enhance resistance to tissue-bound peptidases and retain activity in a number of insect kinin bioassays and/or on expressed receptors. Three of the biostable analogs demonstrated antifeedant activity, with a marked reduction in honeydew formation observed after 1 day, and very high mortality. In contrast, an unmodified, parent insect kinin and two other analogs containing some of the same structural components that promote biostability are inactive. The most active analog, double-Aib analog K-Aib-1 ([Aib]FF[Aib]WGa), featured aphicidal activity calculated at an LC50 of 0.063 nmol/ul (0.048 ug/ul) and an LT50 of 1.68 days, matching the potency of some commercially available aphicides. The mechanism of this activity has yet to be established. The aphicidal activity of the biostable insect kinin analogs may result from disruption of digestive processes by interfering with gut motility patterns, digestive enzyme release, and/or with fluid cycling in the gut; all processes shown to be regulated by the insect kinins in other insects. The active insect kinin analogs represent potential leads in the development of selective, environmentally friendly pest aphid control agents.