GPCR-based bioactive peptide screening using phage-displyed peptides and an insect cell system for insecticide discovery
2021
Choi, Man Yeon | Meer, Robert K.
Discovery of new insecticides improves insect pest management (IPM) but is a long iterative process with low chances of success and high risk. For over two decades, insect neuropeptides (NPs) and their G-protein coupled receptors (GPCRs) have been considered as biological targets for discovery of new specific classes of pesticides because they are involved in almost all physiological processes during insect life stages. A key roadblock to success is how to efficiently screen large chemical libraries, including natural products for active compounds. New technologies, such as 'omics' and many biological tools are now available and should facilitate development of a new approach. In this study, we report a novel GPCR-based screening technology using a phage peptide library and a biopanning method in an insect cell system. This report provides the first proof-of-concept for the development of novel IPM strategies using neuropeptides and GPCRs. Using the fire ant as a model system, bioactive peptides were isolated and identified. The novel small peptides interfere with the target GPCR-ligand functions. Therefore, we refer to this new mechanism as "receptor interference" (Receptor-i). The GPCR-based bioactive screening suggests multiple advantages, including a manageable size (20-30 genes) of target genes, rapid screening process, and flexible delivery methods such as topical, ingestion, and plant-incorporated protectants as a Bt toxin alternative.
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