Andrei P. Drabovich; Maxim V. Berezovski; Michael U. Musheev; Sergey N. Krylov
Anal. Chem., 2009, 81(1), 490-494
https://doi.org/10.1021/ac8023813

Abstract

The development of drugs and diagnostics with desirable characteristics requires smart small-molecule ligands—ligands with predefined binding parameters of interaction with the target. Here, we propose a general approach for selection of such ligands from highly diverse combinatorial libraries of small molecules by methods of kinetic capillary electrophoresis (KCE). We deduct three fundamental requirements for the combinatorial library to suit the KCE-based selection of smart ligands and suggest a universal design of the library for selecting smart small-molecule ligands: every small molecule in the library is tagged with DNA that encodes the structure of the molecule. Finally, we use several DNA-tagged small molecules, which represent a hypothetical library, to prove experimentally selection of smart small-molecule ligands by the proposed approach.