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National Academy of Sciences, Proceedings of the National Academy of Sciences, 46(105), p. 17670-17675, 2008

DOI: 10.1073/pnas.0805130105

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High-throughput sequencing allows the identification of binding molecules isolated from DNA-encoded chemical libraries

Journal article published in 2008 by Luca Mannocci, Yixin Zhang, Jörg Scheuermann ORCID, Markus Leimbacher, Gianluca De Bellis, Ermanno Rizzi, Christoph Dumelin, Samu Melkko, Dario Neri
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

DNA encoding facilitates the construction and screening of large chemical libraries. Here, we describe general strategies for the stepwise coupling of coding DNA fragments to nascent organic molecules throughout individual reaction steps as well as the first implementation of high-throughput sequencing for the identification and relative quantification of the library members. The methodology was exemplified in the construction of a DNA-encoded chemical library containing 4,000 compounds and in the discovery of binders to streptavidin, matrix metalloproteinase 3, and polyclonal human IgG.