Design and synthesis of aromatic inhibitors of anthranilate synthase |
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Authors: | Payne Richard J Bulloch Esther M M Abell Andrew D Abell Chris |
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Affiliation: | Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UKCB2 1EW. |
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Abstract: | 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 microM. The exception was 3-(1-carboxy-ethoxy) benzoic acid, (C-4 = H), for which K(I)= 2.4 microM. 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. |
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