|Nachman, Ronald - Ron|
Submitted to: European Peptide Symposium
Publication Type: Proceedings
Publication Acceptance Date: 1/12/2007
Publication Date: 9/10/2007
Citation: Lodyga-Chruscinska, E., Oldziej, S., Micera, G., Sanna, D., Chruscinski, L., Kaczmarek, K.J., Nachman, R.J., Zabrocki, J. 2007. Potential metal atom binding sites in insect kinin analogs. In: Proceedings of the European Peptide Symposium, September 6-8, 2006, Gdansk, Poland. p. 150-151. 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 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 agricultural or medical pest in such a way as to either over-activate or block critical, neuropeptide-regulated life functions. We report on an investigation into the role of dissolved copper in the specific shapes that a mimic of the insect kinin neuropeptides adopt to interact and activate their respective active sites within the target pests. This discovery will aid in the design of neuropeptide-like compounds capable of disrupting critical life functions in insects. This work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling insect pests in an environmentally friendly fashion.
Technical Abstract: Potentiometric and spectroscopic data, including CD and EPR results, as well as theoretical calculations have shown that the insertion of (2R,4R)-4-aminopyroglutamate (apy), a novel cis-peptide bond mimic, in the insect kinin peptide, Ac-Arg-Phe-apy-Trp-Gly-NH2 leads to a very effective chelating agent towards Cu(II) ions at physiological and basic pH ranges. The 4-aminopyroglutamate motif induces a specific peptide conformation which favors the formation of one or two stable chelating rings stabilizing a bent structure, with the coordination of 3N-type or 4N-type in the metallopeptide molecule. It is worth noting that the copper(II) bonding does not undergo hydrolysis even at a very high pH range.