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Oligo-2'-fluoro-2'-deoxynucleotide N3'-->P5' phosphoramidates: synthesis and properties
1Lynx Therapeutics, Inc, Hayward, CA 94545, USA.
Nucleic Acids Research
|August 1, 1996
Summary
New 2'-fluoro-2'-deoxy-pyrimidine nucleoside phosphoramidates offer enhanced stability for nucleic acid duplexes. These modified oligonucleotides show promise for diagnostic and antisense therapeutic applications.
Area of Science:
- Oligonucleotide Chemistry
- Medicinal Chemistry
- Molecular Biology
Background:
- Oligonucleotides are crucial in diagnostics and therapeutics.
- Modifications are needed to enhance stability and delivery.
- Phosphoramidate linkages offer potential for improved properties.
Purpose of the Study:
- To synthesize uniformly modified oligodeoxyribonucleotide N3 ogether-->P5' phosphoramidates.
- To evaluate the stability and duplex formation of these modified oligonucleotides.
- To explore their potential in diagnostic and therapeutic applications.
Main Methods:
- Synthesis via an efficient interphase amidite transfer reaction.
- Utilizing solid phase-supported nucleosides and phosphoramidite donors.
- Oxidation with aqueous iodine to form internucleoside phosphoramidate diesters.
Main Results:
- Modified oligonucleotides formed extremely stable duplexes with DNA and RNA.
- Melting temperatures (Tm) increased by approximately 4-5°C per modification.
- Compounds exhibited high resistance to enzymatic hydrolysis and acidic conditions.
Conclusions:
- 2 ogether'-fluoro-2 ogether'-deoxy-pyrimidine nucleoside phosphoramidates demonstrate superior stability.
- Enhanced duplex stability and nuclease resistance suggest significant potential.
- These modifications are promising for developing advanced diagnostic tools and antisense therapies.