Dynamic template-assisted strategies in fragment-based drug discovery.
Fragment-based methods for drug discovery are increasingly popular because they provide drug leads with greater ligand efficiency than conventional high-throughput screening. However, established methods for fragment detection do not address the central question in fragment-based ligand discovery: how can a primary ligand be optimally extended by a secondary fragment? Dynamic screening methods solve this issue by using a protein target as a template for ligand assembly, thus yielding high-affinity binders from low-affinity fragments. This review summarizes recent work on dynamic screening methodology, which resulted in the development of several high-affinity binders for various targets. Strengths and limitations of the published approaches are discussed and possible contributions of dynamic screening methodology to the drug discovery process are highlighted.
Schmidt
Marco F
MF
Department of Medicinal Chemistry, Leibniz-Institute of Molecular Pharmacology, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Rademann
Jörg
J
D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*
D008024:Ligands; D011506:Proteins
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