Substrate and reaction intermediate mimics as inhibitors of 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase

Abstract

3-Deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) synthase catalyses the aldol-like addition of phosphoenolpyruvate (PEP) to D-erythrose 4-phosphate in the first step of the shikimate pathway to aromatic amino acids. A series of compounds, designed to mimic intermediates in the enzyme-catalysed reaction, have been synthesised and tested as inhibitors for the DAH7P synthase from Escherichia coli. The most potent inhibitor was the vinyl phosphonate, (E)-2-methyl-3-phosphonoacrylic acid, with a K_i of 4.7 µM.