Influence of 2 '-Fluoro versus 2 '-O-Methyl Substituent on the Sugar Puckering of 4 '-C-Aminomethyluridine
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Title |
Influence of 2 '-Fluoro versus 2 '-O-Methyl Substituent on the Sugar Puckering of 4 '-C-Aminomethyluridine
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Creator |
GORE, KR
HARIKRISHNA, S PRADEEPKUMAR, PI |
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Subject |
FREE-ENERGY CALCULATIONS
NUCLEIC-ACIDS MODIFIED OLIGONUCLEOTIDES STRUCTURAL-PROPERTIES FORCE-FIELD RNA DNA NUCLEOSIDES THERAPEUTICS THYMIDINES |
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Description |
Herein, we report the synthesis of 4'-C-aminomethyl-2'-deoxy-2'-fluorouridine, a therapeutically appealing RNA modification. Conformational analysis by DFT calculations and molecular dynamics simulations using trinucleotide model systems revealed that modified sugar adopts C3'-endo conformation. In this conformer, a weak intramolecular C-H center dot center dot center dot F H-bond between the hydrogen atom of the 4'-C-CH2 group and the F atom at the 2' position is observed. Comparative studies with, unmodified, 2'-fluoro-, 2'-O-methyl-, and 4'-C-aminomethyl-2'-O-methyluridine showed the chemical nature of 2'-substituent dictates the sugar puckering of 2',4' modified nucleotides.
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Publisher |
AMER CHEMICAL SOC
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Date |
2014-10-16T13:25:58Z
2014-10-16T13:25:58Z 2013 |
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Type |
Article
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Identifier |
JOURNAL OF ORGANIC CHEMISTRY, 78(19)9956-9962
http://dx.doi.org/10.1021/jo4012333 http://dspace.library.iitb.ac.in/jspui/handle/100/15661 |
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Language |
en
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