Chimeric oligonucleotides based on 2"-O-modified oligoribonucleotides with the terminal 3"—3" internucleotide linkage as potential inhibitors of MDR 1 gene expression

Chimeric constructs were synthesized based on oligoribonucleotides modified at the 2"-position of the ribose (2"-O-tetrahydropyranyl- or 2"-O-methyl-) and at the 3"-terminus of the oligonucleotide chain (terminal 3"—3" internucleotide linkage), which are complementary to a region of MDR 1 mRNA. A comparative study of the properties of these chimeric constructs was performed. The chimeric oligomers with the modified 3"-terminus are characterized by high stability with respect to 3"-exonucleases, form stable complementary complexes with RNA, and can activate RNase H in a duplex with RNA.