Diversity-oriented synthesis encoded by deoxyoligonucleotides
Name
s41467-023-40575-5.pdf
Description
Published version
Size
3.45 MB
Format
Adobe PDF
Checksum (MD5)
34c3376cd118dc0be0c075d7860d2b75
Date Issued
2023
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Hudson, L., Mason, J.W., Westphal, M.V. et al. Diversity-oriented synthesis encoded by deoxyoligonucleotides. Nat Commun 14, 4930 (2023).
Version
Final published version
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 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.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/s41467-023-40575-5
