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Nature Medicine 9, 118 - 122 (2003)
doi:10.1038/nm0103-118

Advances in the use of synthetic combinatorial chemistry: Mixture-based libraries

Clemencia Pinilla1,2, Jon R. Appel1, Eva Borràs1 & Richard A. Houghten1,2


The conceptual and technical approaches that led to the explosive growth of combinatorial chemistry began approximately 20 years ago. In the past decade, combinatorial chemistry has continued to expand with new chemistries, technological improvements and, most importantly, a clear demonstration of its utility in the identification of active compounds for research and drug-discovery programs. This article describes the conceptual and practical breakthroughs that have been critical for the development of synthetic combinatorial methods and includes the most recent developments and applications of mixture-based combinatorial libraries.


Combinatorial techniques have their origins in Merrifield's seminal solid-phase synthesis of peptides in 1963 (refs. 1 and 2) and have been greatly accelerated by the parallel solid-phase synthesis methods developed during the mid-1980s.

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