On-line electrochemistry-bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors.

ABSTRACT: In this study, an integrated approach is developed for the formation, identification and biological characterization of electrochemical conversion products of p38α mitogen-activated protein kinase inhibitors. This work demonstrates the hyphenation of an electrochemical reaction cell with a continuous-flow bioaffinity assay and parallel LC-HR-MS. Competition of the formed products with a tracer (SKF-86002) that shows fluorescence enhancement in the orthosteric binding site of the p38α kinase is the readout for bioaffinity. Parallel HR-MS(n) experiments provided information on the identity of binders and non-binders. Finally, the data produced with this on-line system were compared to electrochemical conversion products generated off-line. The electrochemical conversion of 1-{6-chloro-5-[(2R

SUBMITTER: Falck D 

PROVIDER: S-EPMC3314180 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature