title: Mannitol Bis-phosphate Based Inhibitors of Fructose 1,6-Bisphosphate Aldolases.
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.
authors.affiliation: ECBB, ICMMO (UMR 8182), LabEx LERMIT, Université Paris-Sud , UMR 8182, F-91405 Orsay, France.
authors.forename: Charles-Gabin
authors.initials: CG
authors.lastname: Mabiala-Bassiloua
authors.affiliation: Biochimie, Université de Montréal , CP 6128, Stn Centre-Ville Montréal, PQ H3C 3J7 Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Arthus-Cartier
authors.affiliation: Research Unit for Tropical Diseases, de Duve Institute , TROP 74.39, Avenue Hippocrate 74, B-1200 Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Hannaert
authors.affiliation: ECBB, ICMMO (UMR 8182), LabEx LERMIT, Université Paris-Sud , UMR 8182, F-91405 Orsay, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Thérisod
authors.affiliation: Biochimie, Université de Montréal , CP 6128, Stn Centre-Ville Montréal, PQ H3C 3J7 Canada.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Sygusch
authors.affiliation: ECBB, ICMMO (UMR 8182), LabEx LERMIT, Université Paris-Sud , UMR 8182, F-91405 Orsay, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Thérisod
keywords: Selective inhibitors; Trypanosoma brucei; fructose bis-phosphate aldolase; glycolysis; microbial enzymes