|Coast, Geoffrey - UNIV OF LONDON|
|Fehrentz, Jean-Alain - FACULTE DE PHARMACIE|
|Kaczmarek, Krzystoff - TECHNICAL UNIV, POLAND|
|Zabrocki, Janusz - TECHNICAL UNIV, POLAND|
|Martinez, Jean - FACULTE DE PHARMACIE|
Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 5, 2003
Publication Date: October 1, 2003
Citation: Nachman, R.J., Coast, G.M., Fehrentz, J., Kaczmarek, K., Zabrocki, J., Pryor, N.W., Martinez, J. 2003. A C-terminal insect kinin analog enhances inhibition of weight gain and induces significant mortality in Helicoverpa zea. Peptides. 24:1615-1621. 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 more strongly with the active site within the pest insect. We report on the development of an innovative mimic that features both enhanced enzyme resistance and an ability to interact more intensely with the internal active sites associated with maintenance of proper water balance and digestive enzyme release. The mimic magnifies the water-elimination and digestive enzyme-release inhibition effects of the natural neuropeptides to such an extent that a majority of the treated corn earworm larvae die. The corn earworm is an important agricultural pest. The work brings us a major 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 first reported examples of C-terminal aldehyde analogs of an insect neuropeptide are described. They are hexapeptide insect kinin analogs Boc-VFFPWG-H and Fmoc-RFFPWG-H. Activity observed for these modified analogs in an in vitro insect diuretic assay confirms that the C-terminal aldehyde group is tolerated by an insect kinin receptor. The two analogs demonstrate greatly enhanced activity over standard C-terminal amide insect kinins in a larval weight gain inhibition assay in the corn earworm, Helicoverpa zea. The development of larvae is so retarded by treatment with Boc-VFFPWG-H that significant increases in mortality are observed at doses of 500 pm (45%) and 5 nm (67%). Boc-VFFPWG-H represents a lead analog in the development of novel, environmentally-friendly pest insect management agents based on the insect kinin class of neuropeptides.