Mechanistically Defined Epoxide- and Aziridine-2-carboxamide Electrophiles Enable Stereoselective Covalent Ribonucleic Acid Modulation
and in cells, while structure-guided placement on a flavin scaffold yields stereoselective covalent modulators of the flavin mononucleotide riboswitch with validated reaction site and cellular activity. Together, this work demonstrates epoxide- and aziridine-2-carboxamides as a versatile platform for covalent RNA targeting and provides a general framework for the rational design of stereochemically controlled RNA-reactive small molecules.
Authors
- Robert Batey (ORCID: https://orcid.org/0000-0002-1384-6625)
- Matthew D. Disney (ORCID: https://orcid.org/0000-0001-8486-1796)
- Xueyi Yang (ORCID: https://orcid.org/0000-0002-0207-5538)
- Noah A. Springer (ORCID: https://orcid.org/0000-0001-8868-0415)
- Chungen Li (ORCID: https://orcid.org/0000-0001-7013-8935)
- Kyle A. Dickerson
- Nikhil C. Munshi
- Jingsong Shan
Institutions
- Scripps Research Institute (US)
- Harvard University (US)
- University of Colorado System (US)
- Dana-Farber Cancer Institute (US)
- Institut thématique Génétique, génomique et bioinformatique (FR)
- Scripps (United States) (US)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2026-04-16
- DOI
- https://doi.org/10.1021/jacs.6c01015
- Primary Topic
- Click Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke