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

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.

Automated summary

The fluoro-modification at the 2'-position of L-cytidine in L-nucleic acids does not disrupt their thermostabilities and maintains structural integrity, allowing it to form a Watson-Crick base pair with L-guanosine. This provides a useful biochemical strategy for investigating L-nucleic acids in advanced molecular therapy.