Chemical modifications of oligonucleotides. (A) Common modifications of the phosphodiester linkage, sugar, and bases moieties are depicted. Note that 2′-O methyl sugar modifications confer stability to single-stranded RNases but not DNases. They do not allow binding of RNase H either. The propynl pyrimidines demonstrate enhanced binding to RNA but cannot permeate membranes. (B) N3-5P phosphoramidates and peptide nucleic acid backbone modifications confer enhanced stability and RNA binding. However, the latter do not permeate membranes and neither activates RNase H.