Rational, Structure-Guided Design of Small Molecule Covalent Translation Inhibitors Targeting mRNA
- Identifying structured regions in mRNA as small molecule targets using cryoEM
- Using 3D information to locate small molecule binding site and understand effect of small molecule binding on RNA structure
- Dependence of translation inhibition on binding site induced proximity and proper orientation of electrophile within binding site
- Importance of using cooler electrophiles when designing covalent translation inhibitors