Biostable and PEG polymer-conjugated insect pyrokinin analogs demonstrate antifeedant activity and induce high mortality in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae)

Abstract The pyrokinins (PK) 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-NH 2 ) and PEGylated analog PK-dF-PEG 8 [(P 8 )-YF[dF]PRL-NH 2 ], featured aphicidal activity calculated at LC 50 's of 0.042 nmol/μl [0.029 μg/μl] (LT 50 of 1.0 day) and 0.126 nmol/μl (LT 50 of 1.3 days), respectively, matching the potency of some commercially available aphicides. Notably, a PEGylated analog of a PK antagonist can block over 55% of the aphicidal effects of the potent PK agonist PK-Oic-1 , suggesting that the aphicidal effects are mediated by a PK receptor. 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 PKs in other insects. The active PK analogs represent potential leads in the development of selective, environmentally friendly aphid pest control agents.