DNA antisense oligonucleotides

Oblimersen sodium is a DNA antisense oligonucleotide designed to specifically bind to human bcl-2 mRNA, resulting in catalytic degradation of bcl-2. This results in decreased translation of the protein Bcl-2, which is a cellular antiapoptotic protein. Thus, oblimersen enhances sensitivity to chemotherapy by shifting the intracellular balance to a state in which the cells are more likely to be killed by apoptosis. Currently, it is used in combination chemotherapy for treating advanced melanoma. 

A test case for modeling chemical changes to DNA Phosphoramidate modified DNA antisense oligonucleotides. 

Sauer M., Brecht A., Charisse K., Stemmier I., Gauglitz G. and Bayer E., Interaction of Chemically Modified Antisense Oligonucleotides with Sense DNA A Label-Free Interaction Study with Reflectometric Interference Spectroscopy, Anal Chem 1999 71 2850. 

Dean N, McKay R, Miraglia L, Howard R, Cooper S, Giddings ], Nicklin P, Meister L, Ziel R, Geiger T, Muller M, Fabbro D (19 ) Iidiibition of growth of human tumor cell lines in nude mice by an antisense oligonucleotide inhibitor of protein kinase C-a expression. Cancer Res 56 3499-3507 Defranco AL (1991) Immunosuppressants at work. Nature 352 754-755 De las Alas MM, Aebi S, Fink D, Howell SB, Los G (1997) Loss of DNA mismatch repair effects on the rate of mutation to drug resistance. J Natl Cancer Inst 89 1537-1541... 

Ac, acetyl AONs, antisense oligonucleotides B, boat Bn, benzyl Bz, benzoyl C, chair CD, circular dichroism CO, carbon monoxide ConA, concanavalin A DAST, diethylaminosulfur trifluoride DFT, density functional theory DMDO, dimethyldiox-irane DMT, dimethoxytriphenylmethyl DNA, deoxyribonucleic acid dsDNA, double-stranded DNA E, envelope Fmoc, fluorenylmethyloxycarbonyl GlcNAc, /V-acetylglucosamine ITC, isothermal titration calorimetry kcat, catalytic rate constant Aa, association constant K, inhibition constant KM, Michaelis constant LiSPh, lithium thiophenolate LPS, lipopolysaccharide pM, micromolar MMT,... 

Translation arrest or nuclease digestion by exogenously applied antisense oligonucleotides or by antisense mRNA produced from DNA delivered by a plasmid. Heterogeneous nuclear RNA is hnRNA. 

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