2'-Spiro ribo- and arabinonucleosides: synthesis, molecular modelling and incorporation into oligodeoxynucleotides. 2003

B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, DK-5230 Odense M, Denmark.

We have synthesized four conformationally restricted bicyclic 2'-spiro nucleosides via 2'-C-allyl nucleosides as key intermediates. The ribo-configured 2'-spironucleosides 9b and 14b were obtained by a convergent strategy starting from 2-ketofuranose 1 whereas the arabino-configured 2'-spironucleosides 21 and 27 were obtained by a linear strategy with a 2'-ketouridine derivative as starting material. The furanose ring of 9b/14b adopts N-type conformations whereas the furanose ring of 21/27 exists as an N<==>S equilibrium. These compounds showed no anti-HIV-1 activity or cytotoxicity. Incorporation of the four 2'-spironucleosides (as monomers X4 and X5) into oligodeoxynucleotides was accomplished using the phosphoramidite approach on an automated DNA synthesizer. Irrespective of monomeric configuration, hybridization studies revealed that these 2'-spironucleotide monomers (X4 and X5) induce decreased duplex thermostabilities compared with the corresponding DNA:DNA and DNA:RNA duplexes. Molecular modelling indicated that steric constraints are a possible reason for the lowered binding affinities of the modified oligodeoxynucleotides towards complementary single-stranded DNA and single-stranded RNA complements.

UI MeSH Term Description Entries
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D009838 Oligodeoxyribonucleotides A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D001087 Arabinonucleosides Nucleosides containing arabinose as their sugar moiety. Arabinofuranosylnucleosides
D012313 RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed) RNA, Non-Polyadenylated,Ribonucleic Acid,Gene Products, RNA,Non-Polyadenylated RNA,Acid, Ribonucleic,Non Polyadenylated RNA,RNA Gene Products,RNA, Non Polyadenylated
D013141 Spiro Compounds Cyclic compounds that include two rings which share a single atom (usually a carbon). The simplest example of this type of compound is Spiro[2.2]pentane, which looks like a bow tie. Compounds, Spiro
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV

Related Publications

B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
December 2008, Current protocols in nucleic acid chemistry,
B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
March 1989, Nucleic acids research,
B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
September 1968, Proceedings of the National Academy of Sciences of the United States of America,
B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
September 2006, Bioorganic & medicinal chemistry,
B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
June 2010, Current protocols in nucleic acid chemistry,
B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
August 2009, Nucleosides, nucleotides & nucleic acids,
B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
August 2018, ChemistrySelect,
B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
November 2002, Current protocols in nucleic acid chemistry,
B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
January 1990, Chemical research in toxicology,
B Ravindra Babu, and Lise Keinicke, and Michael Petersen, and Claus Nielsen, and Jesper Wengel
May 2009, The Journal of organic chemistry,
Copied contents to your clipboard!