Synthesis and properties of 2'-deoxy-2',4'-difluoroarabinose-modified nucleic acids.

ABSTRACT: We report the synthesis, thermal stability, and RNase H substrate activity of 2'-deoxy-2',4'-difluoroarabino-modified nucleic acids. 2'-Deoxy-2',4'-difluoroarabinouridine (2,'4'-diF-araU) was prepared in a stereoselective way in six steps from 2'-deoxy-2'-fluoroarabinouridine (2'-F-araU). NMR analysis and quantum mechanical calculations at the nucleoside level reveal that introduction of 4'-fluorine introduces a strong bias toward the North conformation, despite the presence of the 2'-βF, which generally steers the sugar pucker toward the South/East conformation. Incorporation of the novel monomer into DNA results on a neutral to slightly stabilizing thermal effect on DNA-RNA hybrids. Insertion of 2',4'-diF-araU nucleotides in the DNA strand of a DNA-RNA hybrid decreases the rate of both h

SUBMITTER: Martinez-Montero S 

PROVIDER: S-EPMC4484724 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature