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United States Department of Agriculture

Agricultural Research Service

Research Project: ECOLOGICALLY-BASED MANAGEMENT OF BOLL WEEVILS AND POST-ERADICATION CROP PESTS Title: Inhibition of PK-PBAN-mediated functions in insects: Discovery of selective and non-selective inhibitors

Authors
item Alstein, Miriam - VOLCANI CENTER, ISRAEL
item Ben-Aziz, Orna - VOLCANI CENTER, ISRAEL
item Zeltzer, Irina - VOLCANI CENTER, ISRAEL
item Bhargava, Kalpana - UNIV OF MISSOURI
item Davidovich, Michael - VOLCANI CENTER, ISRAEL
item Strey, Allison
item Pryor, Nan
item Nachman, Ronald

Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 21, 2006
Publication Date: January 4, 2007
Citation: Alstein, M., Ben-Aziz, O., Zeltzer, I., Bhargava, K., Davidovich, M., Strey, A.A., Pryor, N.W., Nachman, R.J. 2007. Inhibition of PK-PBAN-mediated functions in insects: Discovery of selective and non-selective inhibitors. Peptides. 28:574-584.

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 or medical pest in such a way as to either inhibit or over-stimulate critical neuropeptide-regulated life functions. We report on the development of versions of neuropeptides of the pyrokinin class that have been shown to inhibit the biosynthesis of sex pheromone and two developmental processes in insects of agricultural importance. Some demonstrate non-selective inhibition, while others demonstrate selective inhibition. Selectivity is an important component of successful and safe pest control methodologies. The work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling pest arthropods in an environmentally friendly fashion.

Technical Abstract: The antagonistic properties of a few linear and backbone cyclic (BBC) conformationally constraint peptide libraries and their analogs, were tested for the ability to inhibit pyrokinin/pheromone biosynthesis activating neuropeptide (PK/PBAN) mediated functions: sex pheromone biosynthesis in Heliothis peltigera female moths, cuticular melanization in Spodoptera littoralis larvae, pupariation in the fleshfly Neobellieria bullata and hindgut contraction in Leucophaea maderae, elicited by exogenously injected PBAN, pheromonotropin (PT), leucopyrokinin (LPK), myotropin (MT) or by the endogenous peptides. The data revealed differential inhibitory patterns within the same assay with different elicitors (in both the pheromonotropic and melanotropic assays) and among the different functions and disclosed selective antagonists, hinting at the possibility that the receptors that mediate those functions may differ from one another structurally.

Last Modified: 4/18/2014
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