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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.

SUBMITTER: Mabiala-Bassiloua CG

PROVIDER: S-EPMC4018070 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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

Mabiala-Bassiloua Charles-Gabin CG Arthus-Cartier Guillaume G Hannaert Véronique V Thérisod Hélène H Sygusch Jurgen J Thérisod Michel M

ACS medicinal chemistry letters 20110903 11

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 si ...[more]

PMID: 24900268

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