Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1207107 | Journal of Chromatography A | 2009 | 9 Pages |
Abstract
Focus of this work was the development and characterization of a new immobilized enzyme reactor (IMER) containing human recombinant butyrylcholinesterase (rBChE) for the on-line kinetic characterization of specific, pseudo-irreversible and brain-targeted BChE inhibitors as potential drug candidates for Alzheimer's disease (AD). Specifically, a rBChE-IMER containing 0.99Â U of covalently bound target enzyme was purposely developed and inserted into a HPLC system connected to a UV-vis detector. Selected reversible cholinesterase inhibitors, (â)-phenserine and (â)-cymserine analogues, were then kinetically characterized by rBChE-IMER, and by classical in solution assays and their carbamoylation and decarbamoylation constants were determined. The results support the elucidation of the potency, inhibition duration, mode of action and specific structure/activity relations of these agents and allow cross-validation of the two assay techniques.
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Manuela Bartolini, Nigel H. Greig, Qian-sheng Yu, Vincenza Andrisano,