Synthesis of 2′-Deoxy-2′-fluoro-L-cytidine and Fluorinated L-Nucleic Acids for Structural Studies

Abstract

The unique properties of fluorine atom on nucleic acid backbone can offer stricking functional and structural features. In order to extend the biological applications of L-type nucleic acid, we chemically incorporate the fluoro-modification into 2′-position of L-cytidine, and obtain a series of fluoro-modified L-DNAs/ L-RNAs. Our melting study indicates that the 2′-fluoro-modification does not disrupt the thermostabilities of wild-type L-nucleic acids. Consistently, our X-ray crystal structure reveals that fluoro-moiety cause no structural perturbation, and the fluoro-L-cytidine forms the Watson-Crick base pair with L-guanosine virtually identical to nonmodified L-type CG pair. This fluoro-modified cytidine provides a useful biochemical strategy to investigate L-nucleic acid as advanced molecular therapy.