Synthesis and Structural Characterization of 2′-Deoxy-2′-Methoxy-_L-Cytidine Nucleic Acids

We report here for the first time the synthesis of a novel 2′-methoxy-modified L-cytidine analog and its phosphoramidite, as well as its incorporation into oligonucleotides via solid-phase synthesis. Our measure the thermostability of the modified L-nucleic acids by UV-melting studies, and find out the 2′-methoxy-derivatization enhances the thermostability of the L-duplexes. Consistent with the thermostability result, our X-ray crystal structure study reveals that the 2′-methoxy-L-deoxycytidine forms the Watson-Crick base pair with L-guanosine virtually as the mirror-image fashion of native pair. This novel chemically modified L-cytidine provides a useful biochemical and structural strategy to create mirror-image nucleic acid molecules with expanded functionalities.