Synthesis and evaluation of a new inhibitor of phosphoglucose isomerases:: the enediolate analogue 5-phospho-D-arabinohydroxamate

Designed as a high energy intermediate analogue inhibitor of the potent chemotherapeutic target phosphoglucose isomerases, 5-phospho-D-arabinohydroxamate was efficiently synthesized in a two steps procedure. To date, it proved to be the strongest competitive inhibitor with respect to substrate D-fructose-6-phosphate (K-1 down to 98 nM and K-m/K-i values up to 513). A comparative inhibition study of this compound and other known strong inhibitors on phosphoglucose isomerases from three different sources is also reported. (C) 1998 Elsevier Science Ltd. All rights reserved.