Intermediate analogue inhibitors of mandelate racemase: N-Hydroxyformanilide and cupferron

Jennifer R Bourque; Rodney K M Burley; Stephen L Bearne

doi:10.1016/j.bmcl.2006.09.079

Intermediate analogue inhibitors of mandelate racemase: N-Hydroxyformanilide and cupferron

Bioorg Med Chem Lett. 2007 Jan 1;17(1):105-8. doi: 10.1016/j.bmcl.2006.09.079. Epub 2006 Sep 30.

Authors

Jennifer R Bourque¹, Rodney K M Burley, Stephen L Bearne

Affiliation

¹ Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.

PMID: 17055725
DOI: 10.1016/j.bmcl.2006.09.079

Abstract

Mandelate racemase (MR) catalyzes the 1,1-proton transfer that interconverts the enantiomers of mandelate. The transition state/intermediate analogues N-hydroxyformanilide (K(i)=2.79+/-0.19 microM) and cupferron (K(i)=2.67+/-0.09 microM) are identified as potent competitive inhibitors of MR. The pH-pK(i) profile indicates that MR can bind either the protonated or deprotonated forms of N-hydroxyformanilide, with a 10-fold greater affinity for the latter form.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Enzyme Inhibitors / chemistry*
Formamides / chemistry*
Hydrogen-Ion Concentration
Nitrosamines / chemistry*
Pseudomonas putida / enzymology*
Racemases and Epimerases / antagonists & inhibitors*
Racemases and Epimerases / chemistry
Substrate Specificity

Substances

Enzyme Inhibitors
Formamides
Nitrosamines
Racemases and Epimerases
mandelate racemase
cupferron