As many chemical discovery processes in agrochemical research are based on intact, target organisms, we are often presented with bioactive molecules whose target proteins are unknown.  Many such molecules turn out to share targets with previous commercial pesticides and these targets are relatively straightforward to identify using biochemical displacement of known ligands or in vitro functional assays of known target proteins.  Much more challenging is to identify new target proteins and yet these are likely the most valuable, especially for resistance management.  Here we demonstrate the utility of forward genetics in the nematode C. elegans for identifying the target proteins of insecticidal and nematicidal molecules.  We demonstrate the successful identification of 2 different target proteins, acetyl coA carboxylase & vesicular acetylcholine transporter, and the verification of these results.  With ever cheaper and more rapid sequencing capabilities, we discuss the power of this approach not only for identification of target proteins but also binding sites and even binding modes.

Molecular genetics, a tool for novel MOA identification

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.