Structural, dynamic, and enzymatic properties of mixed alpha/beta-oligonucleotides containing polarity reversals
M W Germann1, J M Aramini, B W Kalisch
1Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia 19107, USA.
Abstract:
We employ NMR structure determination, thermodynamics, and enzymatics to uncover the structural, thermodynamic and enzymatic properties of alpha/beta-ODNs containing 3'-3' and 5'-5' linkages. RNase H studies show that alpha/beta-gapmers that are designed to target erbB-2 efficiently elicit RNase H activity. NMR structures of DNA.DNA and DNA.RNA duplexes reveal that single alpha-anomeric residues fit well into either duplex, but alter the dynamic properties of the backbone and deoxyriboses as well as the topology of the minor groove in the DNA.RNA hybrid.
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