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

Abstract

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.