Design, synthesis and selection of DNA-encoded small-molecule libraries View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-09

AUTHORS

Matthew A Clark, Raksha A Acharya, Christopher C Arico-Muendel, Svetlana L Belyanskaya, Dennis R Benjamin, Neil R Carlson, Paolo A Centrella, Cynthia H Chiu, Steffen P Creaser, John W Cuozzo, Christopher P Davie, Yun Ding, G Joseph Franklin, Kurt D Franzen, Malcolm L Gefter, Steven P Hale, Nils J V Hansen, David I Israel, Jinwei Jiang, Malcolm J Kavarana, Michael S Kelley, Christopher S Kollmann, Fan Li, Kenneth Lind, Sibongile Mataruse, Patricia F Medeiros, Jeffrey A Messer, Paul Myers, Heather O'Keefe, Matthew C Oliff, Cecil E Rise, Alexander L Satz, Steven R Skinner, Jennifer L Svendsen, Lujia Tang, Kurt van Vloten, Richard W Wagner, Gang Yao, Baoguang Zhao, Barry A Morgan

ABSTRACT

Biochemical combinatorial techniques such as phage display, RNA display and oligonucleotide aptamers have proven to be reliable methods for generation of ligands to protein targets. Adapting these techniques to small synthetic molecules has been a long-sought goal. We report the synthesis and interrogation of an 800-million-member DNA-encoded library in which small molecules are covalently attached to an encoding oligonucleotide. The library was assembled by a combination of chemical and enzymatic synthesis, and interrogated by affinity selection. We describe methods for the selection and deconvolution of the chemical display library, and the discovery of inhibitors for two enzymes: Aurora A kinase and p38 MAP kinase. More... »

PAGES

647

Journal

TITLE

Nature Chemical Biology

ISSUE

9

VOLUME

5

Author Affiliations

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nchembio.211

DOI

http://dx.doi.org/10.1038/nchembio.211

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022121817

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19648931


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