4'-C-Trifluoromethyl modified oligodeoxynucleotides: synthesis, biochemical studies, and cellular uptake properties.
Org Biomol Chem
; 17(22): 5550-5560, 2019 06 05.
Article
in En
| MEDLINE
| ID: mdl-31112186
ABSTRACT
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 helical structure perturbation for ODN/RNA duplexes. This type of modification slightly decreases the thermal stability of ODN/RNA duplexes (-1 °C/modification) and leads to improved nuclease resistance. Like the well-known phosphorothioate (PS) modification, heavy 4'-CF3 modifications enable direct cellular uptake of the modified ODNs without any delivery reagents. This work highlights that 4'-CF3 modified ODNs are promising candidates for antisense-based therapeutics, which will, in turn, inspire us to develop more potent modifications for antisense ODNs and siRNAs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligodeoxyribonucleotides
/
Hydrocarbons, Fluorinated
Limits:
Humans
Language:
En
Journal:
Org Biomol Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2019
Document type:
Article
Affiliation country:
China