Document Report Card

ID: ALA2016560

Journal: ACS Med Chem Lett

Title: Mannitol Bis-phosphate Based Inhibitors of Fructose 1,6-Bisphosphate Aldolases.

Authors: Mabiala-Bassiloua CG, Arthus-Cartier G, Hannaert V, Thérisod H, Sygusch J, Thérisod M.

Abstract: Several 5-O-alkyl- and 5-C-alkyl-mannitol bis-phosphates were synthesized and comparatively assayed as inhibitors of fructose bis-phosphate aldolases (Fbas) from rabbit muscle (taken as surrogate model of the human enzyme) and from Trypanosoma brucei. A limited selectivity was found in several instances. Crystallographic studies confirm that the 5-O-methyl derivative binds competitively with substrate and the 5-O-methyl moiety penetrating deeper into a shallow hydrophobic pocket at the active site. This observation can lead to the preparation of selective competitive or irreversible inhibitors of the parasite Fba.

CiteXplore: 24900268

DOI: 10.1021/ml200129s