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Updated: Feb 7, 2026
Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
Mechanistically Defined Epoxide- and Aziridine-2-carboxamide Electrophiles Enable Stereoselective Covalent RNA
Chungen Li1,2, Xueyi Yang1,3, Jingsong Shan1,3
1Department of Chemistry, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, 130 Scripps Way, Jupiter, FL 33458 USA.
Researchers developed novel epoxide and aziridine small molecules for covalent RNA targeting. These compounds selectively modify RNA, offering a new platform for drug discovery and understanding RNA function in cells.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- RNA Therapeutics
Background:
- RNA is a challenging target for small-molecule drugs.
- Existing covalent modifiers lack predictable reactivity and stability.
Purpose of the Study:
- To develop a novel class of covalent RNA-targeting electrophiles.
- To enable structure-guided modification of RNA targets.
Main Methods:
- Synthesis of epoxide- and aziridine-2-carboxamide electrophiles.
- Investigation of reactivity with guanine N7.
- Application to pathogenic repeat RNA and FMN riboswitch.
Main Results:
- Developed tunable electrophiles with controlled reactivity and stability.
- Demonstrated selective covalent modification of r(CUG)exp RNA.
- Created stereoselective covalent modulators of the FMN riboswitch.
Conclusions:
- Epoxide- and aziridine-2-carboxamides represent a versatile platform for covalent RNA targeting.
- Established a framework for rational design of stereochemically controlled RNA-reactive molecules.
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