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Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17670-5. doi: 10.1073/pnas.0805130105. Epub 2008 Nov 10.

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

Author information

1
Institut für Pharmazeutische Wissenschaften Departement für Chemie und Angewandte Biowissenschaften, Eidgenössische Technische Hochschule, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.

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.

PMID:
19001273
PMCID:
PMC2584757
DOI:
10.1073/pnas.0805130105
[Indexed for MEDLINE]
Free PMC Article
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