| _version_ |
1824458051018555392
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| author2 |
Massachusetts Institute of Technology. Department of Chemical Engineering
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| author_facet |
Massachusetts Institute of Technology. Department of Chemical Engineering
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| collection |
MIT
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| description |
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 and derived from DOS, to achieve structural diversity beyond what is possible by varying appendages alone. We also show screening results for three diverse protein targets. We will make this DEL available to the academic scientific community to increase access to novel structural features and accelerate early-phase drug discovery.
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| first_indexed |
2025-02-19T04:19:44Z
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| format |
Article
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| id |
mit-1721.1/158201
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| institution |
Massachusetts Institute of Technology
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| language |
English
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| last_indexed |
2025-02-19T04:19:44Z
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| publishDate |
2025
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| publisher |
Springer Science and Business Media LLC
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| record_format |
dspace
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| spelling |
mit-1721.1/1582012025-02-13T13:37:44Z Diversity-oriented synthesis encoded by deoxyoligonucleotides Massachusetts Institute of Technology. Department of Chemical Engineering 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 and derived from DOS, to achieve structural diversity beyond what is possible by varying appendages alone. We also show screening results for three diverse protein targets. We will make this DEL available to the academic scientific community to increase access to novel structural features and accelerate early-phase drug discovery. 2025-02-13T13:37:43Z 2025-02-13T13:37:43Z 2023 2025-02-12T18:56:02Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/158201 Hudson, L., Mason, J.W., Westphal, M.V. et al. Diversity-oriented synthesis encoded by deoxyoligonucleotides. Nat Commun 14, 4930 (2023). en 10.1038/s41467-023-40575-5 Nature Communications Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Springer Science and Business Media LLC
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| spellingShingle |
Diversity-oriented synthesis encoded by deoxyoligonucleotides
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| title |
Diversity-oriented synthesis encoded by deoxyoligonucleotides
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| title_full |
Diversity-oriented synthesis encoded by deoxyoligonucleotides
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| title_fullStr |
Diversity-oriented synthesis encoded by deoxyoligonucleotides
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| title_full_unstemmed |
Diversity-oriented synthesis encoded by deoxyoligonucleotides
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| title_short |
Diversity-oriented synthesis encoded by deoxyoligonucleotides
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| title_sort |
diversity oriented synthesis encoded by deoxyoligonucleotides
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| url |
https://hdl.handle.net/1721.1/158201
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