Core modified 8–17 DNAzymes with 2′-deoxy-2′-C-methylpyrimidine nucleosides

DELLAFIORE, MARÍA; MONTSERRAT, JAVIER M.; IRIBARREN, ADOLFO M.

BIOORGANIC CHEMISTRY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Nueva York; Año: 2020 vol. 104

0045-2068

The catalytic core of an 8-17 DNAzyme directed against STAT 3 was modified using (2R) and (2S) 2-deoxy-2?-C-methyluridine and cytidine. While 2-deoxy-2-C-methyluridine significantly diminished the catalytic activity, 2?-deoxy-2-C-methylcytidine replacement was better accepted, being the kact of modified DNAzymes at 8- and 11- positions comparable to the non-modified one. When 2-O-methyl and phosphorothioate nucleotides were tested in the binding arms together with core modified DNAzymes the kcat was affected in a non predictable way, emphasizing the fact that both chemical substitutions should be considered globally. Finally, 2-deoxy-2-C-methyl modified DNAzymes stability was assayed finding that the double 2?-C-methyl modification in the catalytic core enhanced 70% the stability against a T47D cell lysate compared to a non-modified control.