Selective Irreversible Inhibition of Fructose 1,6-bisphosphate Aldolase from Trypanosoma Brucei.
From: LSPCMIB, UMR-CNRS 5068, Groupe de Chimie Organique Biologique, Université Paul Sabatier, Bat. IIR1, 118 Route de Narbonne 31062, Toulouse Cedex 9, France.
Journal of medicinal chemistry
- Publish Date: Mar 2006
- ISSN: 0022-2623
- Volume: 49
- Issue: 5
- Pages: 1499-502
- Medium: Print
- Language: English
- Citation (JAMA): Dax Chantal, Duffieux Francis, Chabot Nicolas, et al. Selective Irreversible Inhibition of Fructose 1,6-bisphosphate Aldolase from Trypanosoma Brucei.. J. Med. Chem. Mar 2006;49:1499-502
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.
Mesh Headings (Keywords): Aldehydes, Animals, Fructose-Bisphosphate Aldolase, Kinetics, Models, Molecular, Naphthols, Phosphoric Acid Esters, Schiff Bases, Trypanocidal Agents, Trypanosoma brucei brucei
Check for Full Text / PubMed Unique Identifier (PMID): 16509566
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