Title: Evaluation of insect CAP2b analogs with either an (E)-alkene, cis- or a trans-Pro isostere identifies the Pro orientation of antidiuretic activity Authors
Submitted to: Journal of Peptide Science
Publication Type: Abstract Only
Publication Acceptance Date: April 2, 2012
Publication Date: March 15, 2013
Citation: Kaczmarek, K., Etzkorn, F., Coast, G., Zabrocki, J., Nachman, R.J. 2013. Evaluation of insect CAP2b analogs with either an (E)-alkene, cis- or a trans-Pro isostere identifies the Pro orientation of antidiuretic activity. Journal of Peptide Science. 19:181-183. Interpretive Summary: Insect pests have developed resistance to several conventional pesticides, and new approaches are needed for pest management. Although neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions, the neuropeptides hold little promise as pest control agents because they can be degraded in the target pest. New, selective control agents may be developed by designing mimics of these neuropeptides that resist degradation and either inhibit or over-stimulate critical neuropeptide-regulated life functions. We report on the development of a new analog mimic of the CAP2b neuropeptide class that clearly identifies the 3-D structure adopted by the natural hormones that regulate water balance in stink bugs, important agricultural pests of cotton and soybean. The work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in the management of pest insects in an environmentally friendly fashion.
Technical Abstract: The CAP2b neuropeptide family plays an important role in the regulation of the processes of diuresis and/or antidiuresis in a vareity of insects. In particulare, CAP2b (pELYAFPRVamide) has been shown to elicit antidiuretic activity in the green stink bug Acrostemum hilare, an important pest of cotton and soybean in the southern United States. Analogs of CAP2b containing either an (E)-alkene, cisPro, or a transPro isosteric component were synthesized and evaluated in an in vitro stink bug diuretic assay, which involved measurement of fluid secretions of malpighian tubules isolated from A. hilare. At a concentration of 1 um, the conformationally constrained transPro analog demonstrated significant activity, whereas the cisPro analog failed to elicit any activity. The results provide strong evidence for adoption of a trans orientation for the Pro in CAP2b neuropeptides during interaction with receptors associated with the antidiuretic process in the stink bug. The work further identifies a scaffold with which to design mimetic CAP2b analogs as potential leads in the development of environmentally favorable pest management agents capable of disrupting CAP2b-regulated diuretic systems.