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Purification of Extracellular Trypanosomes, Including African, from Blood by Anion-Exchangers (Diethylaminoethyl-cellulose Columns)
Published on: April 6, 2019
Selective irreversible inhibition of fructose 1,6-bisphosphate aldolase from Trypanosoma brucei
Chantal Dax1, Francis Duffieux, Nicolas Chabot
1LSPCMIB, UMR-CNRS 5068, Groupe de Chimie Organique Biologique, Université Paul Sabatier, Bat. IIR1, 118 Route de Narbonne 31062, Toulouse Cedex 9, France.
Abstract:
An irreversible competitive inhibitor hydroxynaphthaldehyde phosphate was synthesized that is highly selective against the glycolytic enzyme fructose 1,6-bisphosphate aldolase from Trypanosoma brucei (causative agent of sleeping sickness). Inhibition involves Schiff base formation by the inhibitor aldehyde with Lys116 followed by reaction of the resultant Schiff base with a second residue. Molecular simulations indicate significantly greater molecular geometries conducive for nucleophilic attack in T. brucei aldolase than the mammalian isozyme and suggest Ser48 as the Schiff base modifying residue.
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