EPSP SYNTHASE - THE DESIGN AND SYNTHESIS OF BISUBSTRATE INHIBITORS INCORPORATING NOVEL 3-PHOSPHATE MIMICS

Novel aromatic bisubstrate inhibitors of the enzyme EPSP (5-enolpyruvo ylshikimate-3-phosphate) synthase (EC 2.5.1.19) have been designed and synthesized as structural analogs of the single, catalytic intermedia te 1 utilized by the enzyme. These aromatic inhibitors incorporate nov el alpha-hydroxyphosphonates, malonate ethers and alpha-hydroxymalonat es as replacements for the hydrolytically labile 3-phosphate group. Th ese 3-phosphate mimics were much preferred to the corresponding methyl ene and vinylic phosphonates, malonates and phosphonomethyl ethers.