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Title: HAEMOLYMPH AND TISSUE-BOUND PEPTIDASE RESISTANT PSEUDOPEPTIDE MIMETIC ANALOGUES OF THE INSECT ALLATOSTATINS

Author
item Nachman, Ronald
item GARSIDE, CHRIS - UNIVERSITY OF TORONTO
item TOBE, STEPHEN - UNIVERSITY OF TORONTO

Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/21/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary: Insect neuropeptides of the allatostatin family are short chains of amino acids (the building blocks of proteins) that regulate developmental and reproductive processes critical for insect survival. Nevertheless, these insect neuropeptides in and of themselves hold little promise as insect control agents because of their susceptibility to being degraded in the target insect, instability under environmental conditions, and inability t pass through the outside skin (cuticle) of the insect. In this paper, we report on the development of active mimics of the neuropeptides that are resistant to the processes that normally would degrade and destroy them within the insect. We report on the discovery of the first insect neuroeptide mimic with documented resistance to all processes that destroy the natural peptide hormones in the blood or other tissues within the insect. This work leads us one step closer to the development of practical lneuropeptide-like chemicals that will be effective in controlling certain pest insects in an environmentally friendly fashion.

Technical Abstract: While neuropeptides of the allatostatin family inhibit in vitro production of juvenile hormone, which modulates aspects of development and reproduction in the cockroach Diploptera punctata, they are susceptible to inactivation by peptidases in the haemolymph gut, and bound to internal tissues. Patterns of peptidase cleavage were investigated in two allatostatin analogues in which sterically bulky components were incorporated into the active core region to block peptidase attack. The results were used to design and synthesize the first mimetic analogue of an insect neuropeptide resistant to degradation by both haemolymph and tissue-bound peptidases. This pseudotetrapeptide allatostatin mimetic analogue represents a valuable tool to neuroendocrinologists studying mechanisms by which the natural peptides operate and the physiological consequences of challenging an insect with an allatostatin it cannot degrade via peptidase enzymes. Disruption of critical physiological processes modulated by neuropeptides such as the allatostatins via peptidase-resistant mimetic analogues could form the basis for novel pest insect management strategies in the future.