Structural, dynamic, and enzymatic properties of mixed alpha/beta-oligonucleotides containing polarity reversals

We employ NMR structure determination, thermodynamics, and enzymatics to un cover the structural, thermodynamic and enzymatic properties of alpha/beta -ODNs containing 3'-3'and 5'-5' linkages. RNase H studies show that alpha/b eta -gapmers that are designed to target erbB-2 efficiently elicit RNase H activity. NMR structures of DNA . DNA and DNA . RNA duplexes reveal that si ngle alpha -anomeric residues fit well into either duplex, but alter the dy namic properties of the backbone and deoxyriboses as well as the topology o f the minor groove in the DNA . RNA hybrid.