Structural, dynamic, and enzymatic properties of mixed alpha/beta-oligonucleotides containing polarity reversals.
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.
Germann
M W
MW
Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia 19107, USA.
Aramini
J M
JM
Kalisch
B W
BW
van de Sande
J H
JH
D000818:Animals; D004247:DNA / Q000737:chemistry; D004789:Enzyme Activation; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000494:pharmacology; D012313:RNA / Q000737:chemistry; D016914:Ribonuclease H / Q000378:metabolism; D013816:Thermodynamics
D016376:Oligonucleotides, Antisense; D012313:RNA; D004247:DNA; D016914:Ribonuclease H