Resistance towards exonucleases of dinucleotides with stereochemically altered internucleotide phosphate bonds

Kinetic constants for the hydrolytic susceptibility of the internucleotide phosphate bond in normal dinucleotides [e.g., 2′-deoxycytidylyl-(3′>5′)-2′-deoxyuridine (dCpdU) and 2′-deoxyadenylyl-(3′→5′)-2′-deoxycytidine (dApdC)] and isomeric dinucleotides [e.g., 2′-deoxycytidylyl-(3′→5′)-1′-deoxy-2′-isouridine (dCpisodU) and 1′-deoxy-2′-isoadenylyl-(3′→5′)-2′-deoxycytidine (isodApdC)], toward 5′- and 3′-exonucleases, phosphodiesterase I (PDE I) and phosphodiesterase II (PDE II) were experimentally determined and remarkable differences emerged. The study is of importance in the discovery of nuclease-stable inhibitors of HIV integrase, but may also have ramifications in the area of anti-sense oligonucleotides of therapeutic interest.