5-Fluoro-2'-deoxycytidine as a Probe for the Study of B/Z-DNA Transition by 19F NMR Spectroscopy

Andrei Solodinin; Angeline Gautrais; Samuel Ollivier; Hongbin Yan

doi:10.1021/acsomega.9b02461

5-Fluoro-2'-deoxycytidine as a Probe for the Study of B/Z-DNA Transition by ¹⁹F NMR Spectroscopy

ACS Omega. 2019 Nov 15;4(22):19716-19722. doi: 10.1021/acsomega.9b02461. eCollection 2019 Nov 26.

Authors

Andrei Solodinin¹, Angeline Gautrais¹, Samuel Ollivier¹, Hongbin Yan¹

Affiliation

¹ Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, Ontario L2S 3A1, Canada.

Abstract

5-Fluoro-2'-deoxycytidine was synthesized by treating 5-fluoro-2'-deoxyuridine with 2,4,6-trimethylphenol in the presence of 1-methylpyrrolidine and trifluoroacetic anhydride, followed by aminolysis. Among N-acetyl, pivaloyl, and benzoyl, N-acetyl was found to be suitable for the protection of the exocyclic amine of 5-fluoro-2'-deoxycytidine because of the stability of the N ⁴-protected nucleoside under acidic conditions and its ease of removal after solid-phase synthesis. This modified nucleoside was incorporated into d(CG)₆ sequences through the phosphoramidite chemistry-based solid-phase synthesis. Circular dichroism experiments suggest that replacement of 2'-deoxycytidine with 5-fluoro-2'-deoxycytidine does not lead to detectable conformational changes, either in the B- or Z-form. ¹⁹F NMR spectroscopy of d(CG)₆ containing 5-fluoro-2'-deoxycytidine revealed that B/Z-DNA transition induced by sodium chloride is likely initiated at terminal ends, leading to unwinding at the middle of duplexes, and eventual switch of handedness when sodium chloride concentration reaches a threshold value.