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item Nachman, Ronald - Ron
item Kaczmarek, Krysztof
item Williams, Howard
item Coast, Geoffrey
item Zabrocki, Janusz

Submitted to: Biopolymers
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/10/2004
Publication Date: 10/1/2004
Citation: Nachman, R.J., Kaczmarek, K., Williams, H., Coast, G.M., Zabrocki, J. 2004. An active insect kinin analog with 4-aminopyroglutamate, a novel cis-peptide bond, type VI beta-turn motif. Biopolymers. 75:412-419.

Interpretive Summary: Neuropeptides are short chains of amino acids (the building blocks of proteins) that regulate aspects of reproduction, development, water balance and digestion that are critical for insect survival. Nevertheless, these insect peptides in and of themselves hold little promise as insect control agents because of susceptibility to being degraded in the target insect, and inability to pass through the outside skin (cuticle) and/or digestive tract of the insect. We must design neuropeptide mimics that resist degradation by enzymes in the digestive tract and blood of pest insects and interact with the active site within the pest insect in such a way as to either over-activate or block critical, neuropeptide-regulated life functions. This work describes the identification of a new scaffold upon which neuropeptide mimics of the 'insect kinin' class can be designed that protects the parent neuropeptide from enzyme inactivation. In addition, the new mimic provides data that further defines the specific shapes required to either activate or block the active site. This information is invaluable in the design of biostable mimics capable of disrupting digestive and diuretic processes in insects. The work brings us a 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: The insect kinins are potent diuretic peptides that preferentially form a cis-Pro, type VI Beta-turn. An insect kinin analog containing (2S,4S)-4-aminopyroglutamate, a novel cis-peptide bond, type VI Beta-turn motif, demonstrates significant activity in the physiological range in a cricket diuretic assay. This is the first instance of a 4-aminopyroglutamate analog of a peptide with a preference for a type VI turn that demonstrates significant bioactivity. The results provide further confirmatory evidence for the active conformation of the insect kinins, and a new scaffold with which to design biostable, peptidomimetic analogs capable of disrupting critical insect kinin-regulated processes in insects.