Novel epoxide-based glutamate agonist class of pesticide: Synthesis, binding mechanism, and potency
Global food production poses one of the greatest challenges for the planet in coming decades, and synthesis of next generation safer pesticides ranks among the important methods in combating this challenge. The vast majority of pesticides are halogenated lipophilic neurotoxins: highly potent in low concentrations and posing certain risks, such as implication in many neurodegenerative diseases. This study utilized the epoxide ring-opening neurotoxin motif found in the lophotoxin natural product family for the conceptualization of 2-epoxygluteric acid as a model class of next generation neurotoxins. Here, we report the stereo-enhanced synthesis of 2- epoxygluteric acid, the crystal structure of the binding domain of GluR2 bound to 2- epoxygluteric acid at 1.86Å, and electrophysiological potency assays showing the dynamic concentration range of both enantiomers. According to the crystal structure, 2-epoxygluteric acid failed to bind covalently to the receptor; however, it was found to bind non-covalently and cause nerve cord death in the crayfish arthropod model at 20mM.
Biological sciences honors program
B.A. of Biological Sciences
Bachelor of Arts
dissertation or thesis