High-Throughput Synthesis of Diverse Compound Collections for Lead Discovery and Optimization.
Small-molecule intervention of protein function is one central dogma of drug discovery. The generation of small-molecule libraries fuels the discovery pipeline at many stages and thereby resembles a key aspect of this endeavor. High-throughput synthesis is a major source for compound libraries utilized in academia and industry, seeking new chemical modulators of pharmacological targets. Here, we discuss the crucial factors of library design strategies from the perspective of synthetic chemistry, giving a brief historic background and a summary of current approaches. Simple measures of success of a high-throughput synthesis such as quantity or diversity have long been discarded and replaced by more integrated measures. Case studies are presented and put into context to highlight the cross-connectivity of the various stages of the drug discovery process.
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476, Potsdam, Germany. Christoph.Rademacher@mpikg.mpg.de.|Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195, Berlin, Germany. Christoph.Rademacher@mpikg.mpg.de.
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Rademacher
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476, Potsdam, Germany.|Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195, Berlin, Germany.
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Seeberger
D002241:Carbohydrates / Q000138:chemical synthesis; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D055808:Drug Discovery; D010455:Peptides / Q000138:chemical synthesis
D002241:Carbohydrates; D010455:Peptides
Automated synthesis; Drug design; High-throughput synthesis; Library design