End capping of oligonucleotides is crucial for enhancing their stability and therapeutic efficacy by resisting 3’ exonuclease degradation, yet the underlying mechanisms remain elusive. Here, the authors design an epimer of threose nucleic acid by replacing deoxyribose with an α-D-erythrofuranosyl moiety, demonstrating its superior stability and resistance by affecting the binding positions of terminal nucleotides in the phosphodiesterase active site.
- Junlin Wen
- Chunlei Zhang
- Hui Mei
