|Garside, Chris - UNIVERSITY OF TORONTO|
|Tobe, Stephen - UNIVERSITY OF TORONTO|
Submitted to: Journal of Insect Biochemistry and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 25, 2000
Publication Date: N/A
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 such pests. The basic premise of this research is that peptides (short chains of amino acids) serve as internal messengers in insects to regulate vital functions. Peptides themselves are unsuitable for control measures due to their instability to enzymes in the circulator and digestive systems of the insect. New, selective control measures may be developed by designing metabolically stable mimics of these neuropeptides that actively inhibit or over-stimulate functions regulated by them, resulting in disruption of the internal environment of the insect. One of the important pieces of information required to develop neuropeptide-based pest control strategies is to determine the impact of metabolically stable mimics on the bodily functions critical for insect survival. In this paper we report that mimics developed to resist interna forces that inactivate the natural 'allatostatin' peptide regulators can significantly inhibit egg development as well as the production of a hormone critical for development of the adult form from the immature stage of an insect. This work leads us several steps closer to the development of practical neuropeptide-like chemicals that will be effective in controlling certain pest insects in an environmentally friendly fashion.
Technical Abstract: Studies on the catabolism of allatostatins (ASTs) provided the rationale for the design of a series of Dip-allatostatin-derived pseudopeptide mimetic analogues. In vitro, the Dip-ASTs and pseudopeptides show varying degrees of resistance to catabolism and all show significant inhibition of juvenile hormone (JH) biosynthesis. This study was undertaken to determine whether potent Dip-ASTs and/or their pseudopeptide mimetic counterparts caused allatostatic effects in vivo following injection into mated female Diploptera punctata. Animals injected with aqueous solvent or Dip-AST 7 (1-7) N-terminal fragment, which excludes the active core region of the ASTs, were used as controls. An in vitro radiochemical assay revealed that injection of Dip-AST 5, 7 or pseudopeptide analogues 397-2 or AST(b)í2 significantly inhibited the biosynthesis of JH (P<0.05). The results also indicate that basal oocyte growth was significantly inhibited by injection of these same compounds, with the exception of Dip-AST 7 (P<0.05). Analogues 396-1 and 419 did not significantly inhibit rates of JH biosynthesis but did significantly inhibit the growth of basal oocytes. Analyses of feeding, excretion and food absorption/utilization patterns of these same animals suggested that these compounds are not toxic to the insect; rather they directly inhibit the biosynthesis of JH by the corpora allata, and reduce the rate of growth of basal oocytes. Disruption of critical reproductive and/or developmental processes by pseudopeptide analogues of the ASTs could provide novel and selective strategies for future insect pest management.