Receptor-assisted combinatorial chemistry: thermodynamics and kinetics in drug discovery.
Current drug discovery using combinatorial chemistry involves synthesis followed by screening, but emerging methods involve receptor-assistance to combine these steps. Adding stoichiometric amounts of receptor during library synthesis alters the kinetics or thermodynamics of the synthesis in a way that identifies the best-binding library members. Three main methods have emerged thus far in receptor-assisted combinatorial chemistry: dynamic combinatorial libraries, receptor-accelerated synthesis, and a new method, pseudo-dynamic libraries. Pseudo-dynamic libraries apply both thermodynamics and kinetics to amplify library members to easily observable levels, and attain selectivity heretofore unseen in receptor-assisted systems.
Cheeseman
Jeremy D
JD
Department of Chemistry, McGill University, 801 Sherbrooke W., Montréal, QC H3A 2K6, Canada.
Corbett
Andrew D
AD
Gleason
James L
JL
Kazlauskas
Romas J
RJ
D020650:Combinatorial Chemistry Techniques / Q000379:methods; D015195:Drug Design; D007700:Kinetics; D008968:Molecular Conformation; D019151:Peptide Library; D011955:Receptors, Drug / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D019151:Peptide Library; D011955:Receptors, Drug