|Nachman, Ronald - Ron|
Submitted to: Acta Biochimica Polonica
Publication Type: Peer reviewed journal
Publication Acceptance Date: 2/16/2006
Publication Date: 2/16/2006
Citation: Lodyga-Chruscinska, E., Sanna, D., Micera, G., Chruscinska, L., Olejnik, J., Nachman, R.J., Zabrocki, J. 2006. Chelating ability of proctolin tetrazole analogue. Acta Biochimica Polonica. 53:65-72. 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 the neuropeptide proctolin and a mimic 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: The aim of the investigation was to establish a chelating ability of a new proctolin analog of the sequence Arg-Tyr-Leu-psi-[CN4]Ala-Thr towards copper(II) ions. The insertion of the tetrazole moiety into the peptide sequence considerably has changed the coordination ability of the ligand. Potentiometric and spectroscopic (UV-Vis, CD, EPR) results indicate that the incorporation of 1,5-disubstituted tetrazole ring favours the formation of a stable complex form of CuH-1L. This species with 4N coordination type is dominating in the physiological pH region. The tetrazole moiety provides one of these nitrogens. The data indicate that Cu(II) ions are strongly trapped inside a peptide backbone. These findings can serve as important information for modeling the biologically relevant peptide-metal binding sites.