Title: Biostable and PEG polymer-conjugated insect pyrokinin analogs demonstrate antifeedant activity and induce high mortality in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae) Authors
Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 7, 2011
Publication Date: March 15, 2012
Citation: Nachman, R.J., Hamshou, M., Kaczmarek, K., Zabrocki, J., Smagghe, G. 2012. Biostable and PEG polymer-conjugated insect pyrokinin analogs demonstrate antifeedant activity and induce high mortality in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae). Peptides. 34:266-273. 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 neuropeptides of the ‘pyrokinin’ class with enhanced biostability that demonstrate potent aphicidal activity when fed to the pea aphid. Some of the synthetic versions match 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 work brings us several steps 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 pyrokinins are multifunctional neuropeptides found in a variety of arthropod species, including the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae). A series of biostable pyrokinin 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 modified Pro residues Oic or Hyp and or a D-amino acid in key positions to enhance resistance to tissue-bound peptidases and retain activity in a number of PK bioassays. A series of PK analogs conjugated with two lengths of polyethyleneglycol (PEG) polymers were also evaluated in the aphid feeding assay. Three of the biostable PK analogs demonstrated potent antifeedant activity, with a marked reduction in honeydew formation and very high mortality after 1 day. In contrast, a number of unmodified, natural pyrokinins and several other analogs containing some of the same structural components that promote biostability were inactive. Two of the most active analogs, Oic analog PK-Oic-1 (FT[Oic]RL-NH2) and PEGylated analog PK-dF-PEG8 [(P8)-YF[dF]PRL-NH2], featured aphicidal activity calculated at LC50’s of 0.042 nmol/ul [0.029 ug/ul] (LT50 of 1.0 day) and 0.126 nmol/ul (LT50 of 1.3 days), respectively; matching the potency of some commercially available aphicides. The mechanism of this activity has yet to be established, though the aphicidal activity of the biostable analogs may result from disruption of digestive processes by interfering with gut motility patterns, a process shown to be regulated by the pyrokinins in other insects. The active pyrokinin analogs represent potential leads in the development of selective, environmentally friendly pest aphid control agents.