Design, synthesis and selection of DNA-encoded small-molecule libraries. Export

@article{citeulike:6069503, 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.}, author = {Clark, Matthew A. and Acharya, Raksha A. and Arico-Muendel, Christopher C. and Belyanskaya, Svetlana L. and Benjamin, Dennis R. and Carlson, Neil R. and Centrella, Paolo A. and Chiu, Cynthia H. and Creaser, Steffen P. and Cuozzo, John W. and Davie, Christopher P. and Ding, Yun and Franklin, G. Joseph and Franzen, Kurt D. and Gefter, Malcolm L. and Hale, Steven P. and Hansen, Nils J. and Israel, David I. and Jiang, Jinwei and Kavarana, Malcolm J. and Kelley, Michael S. and Kollmann, Christopher S. and Li, Fan and Lind, Kenneth and Mataruse, Sibongile and Medeiros, Patricia F. and Messer, Jeffrey A. and Myers, Paul and O'Keefe, Heather and Oliff, Matthew C. and Rise, Cecil E. and Satz, Alexander L. and Skinner, Steven R. and Svendsen, Jennifer L. and Tang, Lujia and van Vloten, Kurt and Wagner, Richard W. and Yao, Gang and Zhao, Baoguang and Morgan, Barry A.}, citeulike-article-id = {6069503}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nchembio.211}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nchembio.211}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19648931}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19648931}, day = {02}, doi = {10.1038/nchembio.211}, issn = {1552-4469}, journal = {Nature chemical biology}, keywords = {inhibitor, kinase, ma}, month = {September}, number = {9}, pages = {647--654}, posted-at = {2009-11-13 02:01:19}, priority = {2}, publisher = {Nature Publishing Group}, title = {Design, synthesis and selection of DNA-encoded small-molecule libraries.}, url = {http://dx.doi.org/10.1038/nchembio.211}, volume = {5}, year = {2009} }

TY - JOUR ID - citeulike:6069503 L3 - citeulike-article-id:6069503 N2 - 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. IS - 9 JF - Nature chemical biology SN - 1552-4469 EP - 654 TI - Design, synthesis and selection of DNA-encoded small-molecule libraries. PB - Nature Publishing Group VL - 5 SP - 647 KW - inhibitor KW - kinase KW - ma AU - Clark, Matthew AU - Acharya, Raksha AU - Arico-Muendel, Christopher AU - Belyanskaya, Svetlana AU - Benjamin, Dennis AU - Carlson, Neil AU - Centrella, Paolo AU - Chiu, Cynthia AU - Creaser, Steffen AU - Cuozzo, John AU - Davie, Christopher AU - Ding, Yun AU - Franklin, Joseph AU - Franzen, Kurt AU - Gefter, Malcolm AU - Hale, Steven AU - Hansen, Nils AU - Israel, David AU - Jiang, Jinwei AU - Kavarana, Malcolm AU - Kelley, Michael AU - Kollmann, Christopher AU - Li, Fan AU - Lind, Kenneth AU - Mataruse, Sibongile AU - Medeiros, Patricia AU - Messer, Jeffrey AU - Myers, Paul AU - O'Keefe, Heather AU - Oliff, Matthew AU - Rise, Cecil AU - Satz, Alexander AU - Skinner, Steven AU - Svendsen, Jennifer AU - Tang, Lujia AU - van Vloten, Kurt AU - Wagner, Richard AU - Yao, Gang AU - Zhao, Baoguang AU - Morgan, Barry PY - 2009/09/02/ UR - http://dx.doi.org/10.1038/nchembio.211 ER -