Can I read Nanomolar Inhibition of Type II Dehydroquinase Based on the Enolate Reaction Mechanism on EtoBox?

Nanomolar Inhibition of Type II Dehydroquinase Based on the Enolate Reaction Mechanism by Miguel D. Toscano; Richard J. Payne; Akira Chiba; Olivier Kerbarh; Chris Abell is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Nanomolar Inhibition of Type II Dehydroquinase Based on the Enolate Reaction Mechanism about?

## Abstract We describe the rational design of a novel, highly potent inhibitor of type II dehydroquinase, the dicarboxylate **6**. The incorporation of a carboxylate at the 3‐position mimics the putative enolate intermediate in the reaction mechanism, and allows a potential electrostatic binding interaction with the arginine on the active site flap. This results in a 1000‐fold increase in potency, making the dicarboxylate **6** the most potent inhibitor of type II dehydroquinase reported to date, with a high ligand efficiency of −0.68 kcal mol^−1^ per nonhydrogen atom. The systematic dissection of **6** in compounds **7**–**12**, all of which show a drop in potency, confirm the synergistic importance of the two carboxylates, the C3 and C4 hydroxyl groups, and the anhydroquinate ring structure for the potency of **6**.

Who reads Nanomolar Inhibition of Type II Dehydroquinase Based on the Enolate Reaction Mechanism?

Author

Miguel D. Toscano; Richard J. Payne; Akira Chiba; Olivier Kerbarh; Chris Abell

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); Wiley - V C H Verlag GmbbH & Co.; Wiley (ISSN 1860-7179)

Published

2006

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)