Forty years of combinatorial technology

Abstract

Combinatorial technology has been facilitating the synthesis and screening of large molecular libraries containing millions of organic compounds ever since its introduction 40 years ago. It has changed the paradigms of pharmaceutical research from focusing on single compounds to focusing on immense collections of compounds. It inspired the development of dynamic combinatorial libraries, fragment-based drug discovery and virtual library screening. Combinatorial technology was revitalized by the development of DNA encoding. Amplification of DNA oligomers plus next-generation sequencing has made it possible to successfully screen billions of compounds in a single process.

Keywords: Affinity-based selection; Combinatorial chemistry; Combinatorial technology; DNA encoding; Dynamic combinatorial libraries; Fragment-based drug discovery; OBOC libraries; Virtual libraries.