|ZHANG, QIRUI - The Ohio State University|
|DENLINGER, DAVID - The Ohio State University|
|JIANG, HONGBO - Kansas State University|
|PARK, YOONSEONG - Kansas State University|
Submitted to: Amino Acids
Publication Type: Abstract Only
Publication Acceptance Date: 6/29/2015
Publication Date: 8/10/2015
Citation: Nachman, R.J., Zhang, Q., Denlinger, D., Jiang, H., Park, Y. 2015. Development of mimetic analogs of pyrokinin-like neuropeptides to disrupt pest insect physiology/behavior. Amino Acids. 47:1635-1636.
Technical Abstract: Pyrokinin (FXPRLamide) neuropeptides regulate a variety of critical processes and behaviors in insects, though they are unsuitable as tools to arthropod endocrinologists and/or as pest management agents due to sub-optimal biostability and/or bioavailability characteristics. Peptidomimetic analogs can overcome these limitations and can either over-activate or block critical neuropeptide-regulated functions. Diapause hormone (DH), a sub-family of the pyrokinins, terminates diapause in pupae of heliothine insects, important crop pests. Insects enter diapause to escape the debilitating effects of harsh climatic conditions (i.e., winter). Mimetic analogs of DH prevent diapause in pupae that develop from larvae injected with these agents; effectively inducing the pest insects to commit a form of ‘ecological suicide’. Amphiphilic analogs of DH containing different hydrocarbon motifs proved to be topically-active. Evaluation of a series of pyrokinin analogs on an expressed DH receptor (HzDHr) cloned from Helicoverpa zea led to the identification of several superagonists, with greater efficacy than the native peptide; as well as several novel analogs with antagonist activity. A series of five PRXamide pyrokinin-like receptors from the red flour beetle (Tribolium castaneum), including two that show strong affinity to DH, were subjected to ligand-receptor specificity analysis using a series of peptidomimetic ligands. The study identified biostable mimetic analogs that demonstrate agonist properties selective for one DH-like receptor over another; as well as selective antagonism of the CAP2b receptor. The pyrokinin-like CAP2b class of peptides demonstrates diuretic activity in insects, and mimetic agonists and antagonists can disrupt the internal water balance critical to survival of pest insects.