An Enzyme-Targeted Herbicide Design Program Based on EPSP Synthase: Chemical Mechanism and Glyphosate Inhibition Studies

The herbicide markets of the late 1990’s and beyond will demand high performance products with stringent environmental acceptability requirements. We have initiated a multi-disciplinary herbicide discovery program directed toward the inhibition of key plant enzymes as one approach to meet these challenges. Plants contain a variety of biosynthetic pathways which are essential for their growth. Effective, plant-specific enzyme inhibitors offer the opportunity to satisfy the herbicide performance needs of the marketplace while exhibiting favorably low mammalian toxicity properties.1 Our enzyme-targeted research effort systematically integrates mechanistic biochemistry, molecular biology, modeling, inhibitor recognition, and structural biology information with organic synthesis through a series of collaborations within and outside Monsanto. A thorough understanding of the chemical mechanism for a particular enzyme target is an essential first step for the design of potent inhibitors.