|Nachman, Ronald - Ron|
Submitted to: Proceedings of the National Academy of Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/24/2011
Publication Date: 10/11/2011
Citation: Zhang, Q., Nachman, R.J., Kaczmarek, K., Zabrocki, J., Denlinger, D.L. 2011. Disruption of insect diapause using novel agonists and an antagonist of diapause hormone. Proceedings of the National Academy of Sciences. 108:16922-16926. 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. One such life function is the dormant state known as diapause, which is widely exploited by insects to circumvent extreme environmental conditions in winter and other adverse seasons. For an insect to survive, feed and reproduce at the appropriate time of year requires fine coordination of the timing of entry into and exit from diapause. We have developed versions of neuropeptides of the ‘Diapause Hormone’ (DH) class that possess enhanced resistance to degradation and are much more active than DH in terminating diapause. Unlike native DH, one such novel compound that we describe also prevents the entry into diapause when administered to the preceding insect growth stage of Heliothis and Helicoverpa species. In addition, we developed another novel version that blocks the termination of diapause. The results suggest potential for using such agents or next-generation derivatives for pest management.
Technical Abstract: The dormant state known as diapause is widely exploited by insects to circumvent winter and other adverse seasons. For an insect to survive, feed and reproduce at the appropriate time of year requires fine coordination of the timing of entry into and exit from diapause. One of the hormones that regulates diapause in moths is the 24-amino acid neuropeptide, diapause hormone (DH). Among members of the Helicoverpa/Heliothis complex of agricultural pests, DH prompts the termination of pupal diapause. Based on the structure of DH, we designed several agonists that are much more active than DH in breaking diapause. Unlike native DH, one such novel compound that we describe also prevents the entry into pupal diapause when administered to the preceding larval stage that have been environmentally programmed for diapause. In addition, we used the novel antagonist development strategy of incorporating a dihydroimidazoline (‘Jones’), trans-Pro mimetic motif into one of our DH agonists, thereby converting the agonist into a DH antagonist that blocks the termination of diapause. These results suggest potential for using such agents or next-generation derivatives for manipulating populations of pest species.