Diversity-oriented synthesis encoded by deoxyoligonucleotides
Diversity-oriented synthesis encoded by deoxyoligonucleotides
Abstract Diversity-oriented synthesis (DOS)is a powerful strategy to prepare molecules with underrepresented features in commercial screening collections, resulting in the elucidation of novel biological mechanisms. In parallel to the development of DOS, DNA-encoded libraries (DELs) have emerged as an effective, efficient screening strategy to identify protein binders. Despite recent advancements in this field, most DEL syntheses are limited by the presence of sensitive DNA-based constructs. Here, we describe the design, synthesis, and validation experiments performed for a 3.7 million-member DEL, generated using diverse skeleton architectures with varying exit vectors, derived from DOS, to achieve structural diversity beyond what is possible by varying appendages alone. We will make this DEL available to the academic scientific community to increase access to novel structural features and accelerate early-phase drug discovery.
Melillo Bruno、Faust Ann Marie E.、Schreiber Stuart L.、Lim Katherine S.、Poirier Jennifer、Capece John、Clemons Paul A.、Thielman Jonathan R.、Gerry Christopher J.、Xia Guoqin、Osswald Heather L.、Knapp John M.、Tan Zher Yin、Liu Shuang、Reidenbach Andrew G.、Bonazzi Simone、Dumelin Christoph E.、Westphal Matthias V.、Tresco Ben I. C.、Briner Karin、Z¨|cri Fr¨|d¨|ric J.、Schaefer Jonas V.、Ottl Johannes、Smith Nichola J.、Kokkonda Praveen、Richter Matthieu J. R.、Hon C. Suk-Yee、Coley Connor W.、Hudson Liam、Hua Bruce K.、Berst Fr¨|d¨|ric、Mason Jeremy W.、Gampe Christian M.、Bradner James E.
Department of Chemistry, The Scripps Research InstituteNovartis Institutes for BioMedical ResearchChemical Biology and Therapeutics Science Program, Broad Institute||Department of Chemistry and Chemical Biology, Harvard UniversityChemical Biology and Therapeutics Science Program, Broad InstituteNovartis Institutes for BioMedical ResearchNovartis Institutes for BioMedical ResearchChemical Biology and Therapeutics Science Program, Broad InstituteChemical Biology and Therapeutics Science Program, Broad InstituteChemical Biology and Therapeutics Science Program, Broad InstituteDepartment of Chemistry, The Scripps Research InstituteDepartment of Chemistry, The Scripps Research InstituteChemical Biology and Therapeutics Science Program, Broad InstituteChemical Biology and Therapeutics Science Program, Broad InstituteChemical Biology and Therapeutics Science Program, Broad Institute||Department of Chemistry and Chemical Biology, Harvard UniversityChemical Biology and Therapeutics Science Program, Broad InstituteNovartis Institutes for BioMedical ResearchNovartis Institutes for BioMedical ResearchChemical Biology and Therapeutics Science Program, Broad Institute||Novartis Institutes for BioMedical ResearchChemical Biology and Therapeutics Science Program, Broad InstituteNovartis Institutes for BioMedical ResearchNovartis Institutes for BioMedical ResearchNovartis Institutes for BioMedical ResearchNovartis Institutes for BioMedical ResearchNovartis Institutes for BioMedical ResearchChemical Biology and Therapeutics Science Program, Broad InstituteChemical Biology and Therapeutics Science Program, Broad InstituteChemical Biology and Therapeutics Science Program, Broad InstituteChemical Biology and Therapeutics Science Program, Broad Institute||Department of Chemical EngineeringChemical Biology and Therapeutics Science Program, Broad Institute||Novartis Institutes for BioMedical ResearchChemical Biology and Therapeutics Science Program, Broad InstituteNovartis Institutes for BioMedical ResearchChemical Biology and Therapeutics Science Program, Broad Institute||Novartis Institutes for BioMedical ResearchNovartis Institutes for BioMedical ResearchNovartis Institutes for BioMedical Research
生物科学研究方法、生物科学研究技术药学生物化学
Melillo Bruno,Faust Ann Marie E.,Schreiber Stuart L.,Lim Katherine S.,Poirier Jennifer,Capece John,Clemons Paul A.,Thielman Jonathan R.,Gerry Christopher J.,Xia Guoqin,Osswald Heather L.,Knapp John M.,Tan Zher Yin,Liu Shuang,Reidenbach Andrew G.,Bonazzi Simone,Dumelin Christoph E.,Westphal Matthias V.,Tresco Ben I. C.,Briner Karin,Z¨|cri Fr¨|d¨|ric J.,Schaefer Jonas V.,Ottl Johannes,Smith Nichola J.,Kokkonda Praveen,Richter Matthieu J. R.,Hon C. Suk-Yee,Coley Connor W.,Hudson Liam,Hua Bruce K.,Berst Fr¨|d¨|ric,Mason Jeremy W.,Gampe Christian M.,Bradner James E..Diversity-oriented synthesis encoded by deoxyoligonucleotides[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2022.10.16.512431.点此复制
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