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


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.

SUBMITTER: Mannocci L 

PROVIDER: S-EPMC2584757 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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

Mannocci Luca L   Zhang Yixin Y   Scheuermann Jörg J   Leimbacher Markus M   De Bellis Gianluca G   Rizzi Ermanno E   Dumelin Christoph C   Melkko Samu S   Neri Dario D  

Proceedings of the National Academy of Sciences of the United States of America 20081110 46


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 t  ...[more]

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