Characterization of Stereoisomerism of Antisense Oligonucleotides

Abstract

Antisense strategy is one of the promising methods for curing incurable diseases such as cancer and AIDS by regulating gene expression. Oligonucleotides and their analogs have been innovated and used for the purposes. However, stereoisomerism of antisense molecules that intrinsically exists in such molecules contains a crucial problem for the future development of the strategy. In this report, the effects of stereoisomerism on antisense effects were studied by reversed phase HPLC, UV and CD spectroscopy. As antisense molecules, oligonucleoside phosphoramidates and oligonucleoside phosphorothioates both of which contain stereoisomeric modified phosphate linkages, were synthesized and characterized. As results, it was found that there exist large differences in solution structure and that the stereoisomerism may have crucial effect on the antisense gene regulation.