Competitive inhibitors of yeast phosphoglucose isomerase: synthesis and evaluation of new types of phosphorylated sugars from the synthon D-arabinolactone-5-phosphate.
Designed as competitive inhibitors of the isomerization reaction catalyzed by the potential chemotherapeutic target phosphoglucose isomerases (PGI), D-arabinonamide-5-phosphate and D-arabinohydrazine-5-phosphate were synthesized and fully characterized. These new types of phosphorylated sugar derivatives were easily and efficiently obtained in a one-step procedure from the promising synthon D-arabinono-1,4-lactone 5-phosphate. These two compounds proved to be new good competitive inhibitors of yeast PGI with the substrate D-fructose-6-phosphate, though not as strong as D-arabinohydroxamic acid-5-phosphate. Overall, our results are in accord with the postulated 1,2-cis-enediolate species as a probable high-energy intermediate of the PGI-catalyzed reaction.
Hardré
R
R
CNRS, Institut de Chimie Moléculaire d'Orsay, Université de Paris- Sud, France.
Salmon
L
L
D001667:Binding, Competitive; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013403:Sugar Phosphates / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007783:Lactones; D013403:Sugar Phosphates; C122021:arabinonolactone-5-phosphate; D005956:Glucose-6-Phosphate Isomerase