4′‑C‑Trifluoromethyl Modified Oligodeoxynucleotides: Synthesis, Biochemical Studies, and Cellular Uptake Properties
Herein, we report the synthesis of 4′-C-trifluoromethyl (4′-CF3) thymidine (T4′-CF3) and its incorporation into oligodeoxynucleotides (ODNs) through solid-supported DNA synthesis. The 4′-CF3 modification leads to a marginal effect on the deoxyribose conformation and a local helix structure perturbation for ODN/RNA duplexes. This type of modification slightly decreases the thermal stability of ODN/RNA duplexes (-1 °C/modification) and renders improved nuclease resistance. Like the well-known phos-phorothioate (PS) modification, heavy 4′-CF3 modifications enable direct cellular uptake of the modi-fied ODNs without any delivery reagents. This work highlights that 4′-CF3 modified ODNs are promis-ing candidates for antisense-based therapeutics, which will, in turn, inspire us to develop more potent modifications for antisense ODNs and siRNAs.
- This article is part of the themed collection: Chemical biology in OBC