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.