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 (Ki down to 98 nM and Km/Ki 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.
Hardré
R
R
Laboratoire de Chimie Bioorganique et Bioinorganique, CNRS-URA 1384, ICMO, Université Paris-XI, Orsay, France.
Bonnette
C
C
Salmon
L
L
Gaudemer
A
A
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors*; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D005956:Glucose-6-Phosphate Isomerase