title: A novel chiral ligand exchange capillary electrophoresis system with amino acid ionic liquid as ligand and its application in screening D-amino-acid oxidase inhibitors.
abstract: A novel amino acid ionic liquid (AAIL) with L-ornithine (L-Orn) as anion was successfully synthesized, and subsequently applied as an available chiral ligand coordinated with Zn(II) in a chiral ligand exchange capillary electrophoresis (CLE-CE) system for the enantioseparation of dansyl amino acids (Dns-D,L-AAs). The influence of key parameters, such as buffer pH, concentration ratio of Zn(II) to ligand and complex concentration, was investigated in detail. Eleven pairs of Dns-D,L-AAs enantiomers were baseline separated and three pairs were partly separated under the optimum conditions. For exploring its potential application, the quantitative features of this proposed method were studied. Good linearity (r(2) = 0.999) and favorable repeatability (RSD ≤ 3.4%) were obtained by using Dns-D,L-Met as the test analyte. Finally, this method was employed to investigate the inhibition efficiency of d-amino acid oxidase (DAAO) inhibitors, which may pave a new way for the high-throughput screening of enzyme inhibitors and relevant drug discovery.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Mu
authors.forename: Li
authors.initials: L
authors.lastname: Qi
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.forename: Haizhi
authors.initials: H
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Qiao
authors.forename: Huimin
authors.initials: H
authors.lastname: Ma
mesh_terms: D000596:Amino Acids / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D019075:Electrophoresis, Capillary / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D052578:Ionic Liquids; D008024:Ligands; D009952:Ornithine; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D052578:Ionic Liquids; D008024:Ligands; D009952:Ornithine; D003605:D-Amino-Acid Oxidase; D015032:Zinc