THE EVALUATION OF 2'-SUBSTITUTED AND 6'-SUBSTITUTED CARBOCYCLIC NUCLEOSIDES AS BUILDING-BLOCKS FOR ANTISENSE OLIGONUCLEOTIDES

Oligodeoxyribonucleotides incorporating 2'- or B'-alkoxy substituted c arbocyclic nucleotide units are shown to bind to complementary RNA wit h lower affinity than their unmodified parent compounds, while the pre sence of stretches of contiguous 6'-hydroxy substituted building block s enhances RNA-binding affinity. 6'-substituted carbocyclic nucleotide s are generally found to increase oligonucleotide resistance to enzyma tic degradation, the effect being more pronounced for larger substitue nts,