3'-C-Branched LNA-type nucleosides locked in an N-type furanose ring conformation: synthesis, incorporation into oligodeoxynucleotides, and hybridization studies
| Autor: | Jesper Wengel, Michael Meldgaard, Flemming Gundorph Hansen |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
chemistry.chemical_classification
Phosphoramidite Magnetic Resonance Spectroscopy Chemistry Stereochemistry Organic Chemistry Molecular Conformation Oligonucleotides Nucleic Acid Hybridization Protonation Nucleosides General Medicine Spectrometry Mass Fast Atom Bombardment Condensation reaction Branching (polymer chemistry) Ring (chemistry) Furanose Chemical synthesis Nucleobase chemistry.chemical_compound Monomer Furans Alkyl |
| Zdroj: | Meldgaard, M, Hansen, F C & Wengel, J 2004, ' 3'-C-Branched LNA-type nucleosides locked in an N-type furanose ring conformation: Synthesis, incorporation into oligodeoxynucleotides and hybridization studies ', Journal of Organic Chemistry, vol. 69, no. 19, pp. 6310-6322 . https://doi.org/10.1021/jo049159a |
| ISSN: | 0022-3263 |
| Popis: | Three protected 3'-C-branched LNA-type phosphoramidite building blocks 17, 27, and 38, containing furanose rings locked in an N-type conformation, were synthesized from a known 3-C-allyl allofuranose derivative using strategies relying on the introduction of the branching alkyl chain before condensation with the nucleobase. Synthesis of 3'-C-hydroxypropyl derivatives proved superior to synthesis of the 3'-C-hydroxyethyl derivatives, and the former was converted into the corresponding 3'-C-aminopropyl derivatives. Phosphoramidites 27 and 38 were subsequently applied on an automated DNA synthesizer leading to the introduction of three novel 3'-C-branched LNA-type monomers X, Y, and Z into oligodeoxynucleotides and studies of their effect on the hybridization properties. A duplex-stabilizing effect of introducing 3'-C-aminopropyl-LNA monomer Y, relative to 3'-C-hydroxypropyl-LNA monomer X, was observed, especially at low salt conditions. This indicates that the primary amino group of monomer Y is protonated under the hybridization conditions applied and that positioning of this positively charged group in the major groove has a significant duplex stabilizing effect. Monomer Y was by an on-column conjugation method further functionalized by a glycyl unit to give monomer Z that showed a less stabilizing effect than monomer Y. |
| Databáze: | OpenAIRE |
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