Richard J. Payne, Esther M. M. Bulloch, Andrew D. Abell and Chris Abell
Org. Biomol. Chem., 2005,3, 3629-3635
DOI:
10.1039/B510633H,
Paper
Anthranilate synthase catalyses the conversion of chorismate to anthranilate, a key step in tryptophan biosynthesis. A series of 3-(1-carboxy-ethoxy) benzoic acids were synthesised as chorismate analogues, with varying functionality at C-4, the position of the departing hydroxyl group in chorismate. Most of the compounds were moderate inhibitors of anthranilate synthase, with inhibition constants between 20–30 µM. The exception was 3-(1-carboxy-ethoxy) benzoic acid, (C-4 = H), for which KI = 2.4 µM. These results suggest that a hydrogen bonding interaction with the active site general acid (Glu309) is less important than previously assumed for inhibition of the enzyme by these aromatic chorismate analogues.