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Title: Beta-Amino acid analogs of an insect neuropeptide

item Zubrzak, Pawel
item Williams, Howard
item Coast, Geoffrey
item Reyes-rangel, Gloria
item Juaristi, Eusebio
item Zabrocki, Janusz
item Strey, Allison
item Nachman, Ronald - Ron

Submitted to: American Peptide Symposium
Publication Type: Proceedings
Publication Acceptance Date: 6/23/2005
Publication Date: 6/20/2005
Citation: Zubrzak, P., Williams, H., Coast, G.M., Reyes-Rangel, G., Juaristi, E., Zabrocki, J., Strey, A.A., Nachman, R.J. 2006. Beta-Amino acid analogs of an insect neuropeptide. Proceedings of the 19th American Peptide Symposium, New York, NY, June 18-23, 2005. p. 369-370.

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. 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. We report on the development of versions of neuropeptides of the insect kinin class with enhanced biostability via a novel strategy that involves use of non-natural variants of amino acids known as ‘beta’ amino acids. Two of the neuropeptide versions have been shown to be as potent as natural neuropeptides in terms of their ability to regulate water balance in insects. The work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling pest insects in an environmentally friendly fashion.

Technical Abstract: Insect neuropeptides of the insect kinin class share a common C-terminal pentapeptide sequence FX1X2WG-NH2 (X2 = P,S) and regulate such critical physiological processes as water balance and digestive enzyme release. Incorporation of beta-amino acids in peptides can enhance both resistance to peptidase attack and biological activity. The critical residues of F,P and W in the insect kinins were replaced with beta-amino acid and/or their beta-homo-amino acid counterparts and the resulting analogs evaluated in an insect diuretic bioassay. Two of the analogs, featuring replacement of the F and P residues, retain the range of potency of the native insect kinins and represent modifications at two known peptidase hydrolysis sites.