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We constructed a high\u2010quality DNA\u2010encoded chemical library comprising 30\u2009000 drug\u2010like compounds; this was screened in 170 different affinity capture experiments. High\u2010throughput sequencing allowed the evaluation of 120\u2005million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor\u2010associated antigen carbonic anhydrase\u2005IX (CA\u2005IX) and the pro\u2010inflammatory cytokine interleukin\u20102 (IL\u20102) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL\u20102 was confirmed by molecular docking. Our findings suggest that DNA\u2010encoded chemical libraries allow the facile identification of drug\u2010like ligands principally to any protein of choice, including molecules capable of disrupting high\u2010affinity protein\u2013protein interactions.<\/jats:p>","DOI":"10.1002\/chem.201200952","type":"journal-article","created":{"date-parts":[[2012,5,15]],"date-time":"2012-05-15T16:21:40Z","timestamp":1337098900000},"page":"7729-7737","source":"Crossref","is-referenced-by-count":106,"title":["Discovery of Small\u2010Molecule Interleukin\u20102 Inhibitors from a DNA\u2010Encoded Chemical Library"],"prefix":"10.1002","volume":"18","author":[{"given":"Markus","family":"Leimbacher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Mannocci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Stravs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Geppert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Scheuermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisbert","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Neri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,15]]},"reference":[{"key":"e_1_2_6_1_2","first-page":"487","volume":"8","author":"Posner B. 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