Abstract
[structure: see text] Oligonucleotides with a novel, 2'-O-[2-[2-(N,N-dimethylamino)ethoxy]ethyl] (2'-O-DMAEOE) modification have been synthesized. This modification, a cationic analogue of the 2'-O-(2-methoxyethyl) (2'-O-MOE) modification, exhibits high binding affinity to target RNA (but not to DNA) and exceptional resistance to nuclease degradation. Analysis of the crystal structure of a self-complementary oligonucleotide containing a single 2'-O-DMAEOE modification explains the importance of charge factors and gauche effects on the observed antisense properties. 2'-O-DMAEOE modified oligonucleotides are ideal candidates for antisense drugs.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Drug Stability
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Ethane / analogs & derivatives
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Ethane / chemistry*
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Ethers / chemistry*
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Models, Molecular
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Nucleic Acid Conformation
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Nucleic Acid Heteroduplexes / chemistry
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Nucleic Acid Hybridization
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Oligonucleotides, Antisense / chemistry*
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Oligonucleotides, Antisense / metabolism
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Organophosphorus Compounds / chemistry
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Organophosphorus Compounds / metabolism
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Phosphoric Diester Hydrolases / metabolism
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RNA, Complementary / metabolism
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Snake Venoms / enzymology
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Spectrometry, Mass, Electrospray Ionization
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Static Electricity
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Stereoisomerism
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Structure-Activity Relationship
Substances
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2'-O-(2-(2-(N,N-dimethylamino)ethoxy)ethyl)
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Ethers
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Nucleic Acid Heteroduplexes
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Oligonucleotides, Antisense
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Organophosphorus Compounds
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RNA, Complementary
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Snake Venoms
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Phosphoric Diester Hydrolases
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Ethane