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

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 sequenc...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 105; no. 46; pp. 17670 - 17675
Main Authors Mannocci, Luca, Zhang, Yixin, Scheuermann, Jörg, Leimbacher, Markus, De Bellis, Gianluca, Rizzi, Ermanno, Dumelin, Christoph, Melkko, Samu, Neri, Dario
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 18.11.2008
National Acad Sciences
Subjects
Amino acids
Biochemistry
Biological Sciences
Carboxylic acids
Chemical reactions
Chemicals
Deoxyribonucleic acid
DNA
DNA - analysis
Fluorescence
Fluorescence Polarization
Humans
Immunoglobulin G - metabolism
Kinetics
Libraries
Matrix Metalloproteinase 3 - metabolism
Methods
Molecular biology
Molecules
Oligonucleotides
Physical Sciences
Resins
Sequence Analysis, DNA - methods
Sequencing
Small Molecule Libraries - chemistry
Streptavidin - metabolism
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Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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Edited by Jonathan A. Ellman, University of California, Berkeley, CA, and accepted by the Editorial Board September 9, 2008
Author contributions: L.M. and D.N. designed research; L.M., Y.Z., J.S., M.L., and S.M. performed research; L.M., Y.Z., J.S., M.L., G.D.B., E.R., C.D., and S.M. contributed new reagents/analytic tools; L.M., Y.Z., M.L., C.D., and S.M. analyzed data; and D.N. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0805130105