AI Article Synopsis
- DNA-encoded libraries (DELs) are important for discovering small-molecule drugs, but their chemical diversity is restricted to water-friendly reactions to keep DNA tags intact.
- A new workflow using DNA-cationic surfactant complexation allows DELs to operate in dry organic solvents, expanding the range of chemical reactions possible.
- The method is optimized for large-scale production in a 96-well format, facilitating screening and improvement of reactions suitable for DELs in non-aqueous environments.
Article Abstract
DNA-encoded libraries (DELs) are a key technology for identifying small-molecule hits in both the pharmaceutical industry and academia, but their chemical diversity is largely limited to water-compatible reactions to aid in the solubility and integrity of encoding DNA tags. To broaden the DEL chemical space, we present a workflow utilizing DNA-cationic surfactant complexation that enables dissolution and reactions on-DNA in anhydrous organic solvents. We demonstrate its utility by developing DEL-compatible photoredox decarboxylative C(sp)-C(sp) coupling under water-free conditions. The workflow is optimized for the 96-well format necessary for large-scale DEL productions, and it enables screening and optimization of DEL-compatible reactions in organic solvents.
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| http://dx.doi.org/10.1021/acs.orglett.4c01398 | DOI Listing |
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