2-Aminopropane-1,2,3-tricarboxylic acid: Synthesis and co-crystallization with the class A beta-lactamase BS3 of Bacillus licheniformis.
The title compound 4 has been prepared in four steps from ethylglycinate in 63% overall yield. This amino analog of citric acid has been co-crystallized with the class A beta-lactamase BS3 of Bacillus licheniformis and the structure of the complex fully analyzed by X-ray diffraction. Tris-ethyl aminocitrate 3 and the free tris-acid 4 have been tested against a member beta-lactamase from all distinct subgroups. They are novel inhibitors of class A beta-lactamases, still modest but more potent than citrate and isocitrate.
Unité de Chimie Organique et Médicinale, Université catholique de Louvain, Bâtiment Lavoisier, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium.
Joséphine
J
Beck
Eric
E
Sauvage
Paulette
P
Charlier
Jacqueline
J
Marchand-Brynaert
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D001407:Bacillus / Q000201:enzymology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D002412:Cations; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019343:Citric Acid / Q000737:chemistry; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D007523:Isocitrates / Q000737:chemistry; D008956:Models, Chemical; D008968:Molecular Conformation; D010100:Oxygen / Q000737:chemistry; D014233:Tricarboxylic Acids / Q000737:chemistry*; D014961:X-Ray Diffraction; D001618:beta-Lactamases / Q000378:metabolism*
C531397:2-aminopropane-1,2,3-tricarboxylic acid; D001426:Bacterial Proteins; D002412:Cations; D007523:Isocitrates; D014233:Tricarboxylic Acids; D019343:Citric Acid; D001224:Aspartic Acid; C034219:isocitric acid; D001618:beta-Lactamases; D010100:Oxygen