An T.H. Le; Svetlana M. Krylova; Sergey N. Krylov
TrAC, Trends Anal. Chem., 2023, 117061
https://doi.org/10.1016/j.trac.2023.117061

Abstract

Identifying protein binders is the first step in drug discovery. The combinatorial approach, in which a library of compounds is subjected to affinity screening against a target protein, is a major way for identifying protein binders. Oligonucleotide libraries constitute the largest source of material for such affinity screening. Selecting protein binders from such libraries requires a highly efficient method for separation of protein-oligonucleotide complexes from the excess of unbound oligonucleotides. Kinetic Capillary electrophoresis (KCE) is a fast-developing trend in affinity applications. It has the highest reported efficiency of partitioning, but screening oligonucleotide libraries by KCE has many challenges which must be addressed before KCE can compete with conventional surface-based screening. Here we provide the critical analysis of advantages and limitations of KCE in screening oligonucleotide libraries. We identify potential ways of overcoming the limitations in an attempt to direct researchers towards the most important and urgent tasks in this area.