Selection of smart small-molecule ligands: the proof of principle.
The development of drugs and diagnostics with desirable characteristics requires smart small-molecule ligandsligands 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.
Drabovich
Andrei P
AP
Department of Chemistry, York University, Toronto, Ontario M3J1P3, Canada.
Berezovski
Maxim V
MV
Musheev
Michael U
MU
Krylov
Sergey N
SN
D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001710:Biotin / Q000031:analogs & derivatives / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004247:DNA / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D007700:Kinetics; D008024:Ligands; D016133:Polymerase Chain Reaction / Q000379:methods
D052157:Aptamers, Nucleotide; D008024:Ligands; D001710:Biotin; C004749:desthiobiotin; D004247:DNA; D002784:Cholesterol