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. (C) 2003 Elsevier Ltd. All rights reserved.