|ZHANG, QIRUI - The Ohio State University|
|DENLINGER, DAVID - The Ohio State University|
Submitted to: Peptides
Publication Type: Review Article
Publication Acceptance Date: 5/20/2015
Publication Date: 10/15/2015
Citation: Zhang, Q., Nachman, R.J., Denlinger, D.L. 2015. Diapause hormone in the Helicoverpa/Heliothis complex: A review of gene expression, peptide structure and activity, analog and antagonist development, and the receptor. Peptides. 72:196-201.
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. This book chapter reviews the gene blueprint, the neuropeptide structure, and the active site for diapause hormone, which induces agricultural insect pests to enter a state of ‘hibernation’ to circumvent unfavorable seasons. The chapter also reviews development of neuropeptide mimics that can prevent the onset of the protective state of diapause in the corn earworm, inducing the crop pest to commit a form of ‘ecological suicide’. Alternatively, still other mimics can block the activity of the native hormone. The book chapter reviews research results that provide the basis for development of practical neuropeptide-like substances that can effectively control pest insects in an environmentally friendly fashion.
Technical Abstract: This review summarizes recent studies focusing on diapause hormone (DH) in the Helicoverpa/Heliothis complex of agricultural pests. Moths in this complex overwinter in pupal diapause, a form of developmental arrest used to circumvent unfavorable seasons. DH was originally reported in the silkmoth Bombyx mori, a species that relies on DH to induce an embryonic diapause. But, in the case of Helicoverpa/Heliothis, levels of dh transcripts and DH peptides are more abundant in nondiapausing pupae than in diapausing individuals, and DH effectively terminates diapause within a specific temperature range. A structure activity relationship study indicated that the active core of DH is the C-terminal hepta-peptide, LWFGPRLa. We designed and synthesized a first generation of DH agonists and identified two agonists (PK-2Abf and PK-Etz) that were nearly 50- and 13-fold more potent than the native hormone. These studies revealed two structural characteristics of DH and its agonists that are essential for interaction with the receptor: a trans-Pro configuration to form a type I beta-turn and a hydrophobic moiety involved in ligand binding. Modification of DH at the active core yielded a potent DH antagonist (DH-Jo, acetyl-GLWA[Jo]RLa) as well as an antagonist (DH-2Abf-K). Three compounds (Decyl-1963, Dodecyl-1967, Heptyl-1965) were identified as agents capable of penetrating the cuticle of young pupae and thereby preventing the entry into diapause. DH receptor cDNA was cloned and an effective in vitro high throughput screen system was established for future use. This work sets the stage for further development of DH analogs and antagonists that have the potential to disrupt insect diapause as a tool for pest management.