Nucleosides and oligonucleotides containing 1,2,3-triazole residues with nucleobase tethers: Synthesis via the azide-alkyne `click' reaction

Autor(en): Chittepu, Padmaja
Sirivolu, Venkata Ramana
Seela, Frank
Stichwörter: 1,2,3-triazole nucleosides; ANALOGS; base pairing; BASE-PAIRS; Biochemistry & Molecular Biology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; COUMARIN; CYCLOADDITIONS; DESIGN; DNA; FLUORESCENCE; huisgen-meldal-sharpless cycloaddition; oligonucleotides; Pharmacology & Pharmacy; propargylated nucleobases; PYRIMIDINE; SIDE-CHAINS
Erscheinungsdatum: 2008
Herausgeber: PERGAMON-ELSEVIER SCIENCE LTD
Journal: BIOORGANIC & MEDICINAL CHEMISTRY
Volumen: 16
Ausgabe: 18
Startseite: 8427
Seitenende: 8439
Zusammenfassung: 
A series of novel 1,2,3-triazole nucleosides linked to DNA nucleobases were prepared via copper(I)catalyzed 1,3-dipolar cycloaddition of N-9 propargylpurines or N-1 propargylpyrimidines with the tolouyl protected 1-azido-2-deoxyribofuranose 2 followed by treatment with NaOMe/ MeOH or aq NH3. The antiviral activity of such compounds against selected RNA viruses is reported. The strongly fluorescent 1,2,3-triazole compounds 16 and 17 were synthesized from propargylated uracil 1a and propargylated adenine 1c with coumarin azide 15, and the fluorescence properties were studied. The nucleosides 4 and 6 were incorporated into DNA using the phosphoramidite building blocks and employed in solid-phase synthesis. Melting experiments demonstrated that such 1,2,3-triazole nucleosides have a negative impact on the duplex stability when they are placed opposite to the canonical bases as well as abasic sites. The nucleobases attached to the triazole ring cannot involve in the base pair formation with the opposite bases because of the structural variations induced by the triazole ring. The stacking of such nucleosides when positioned at the end of oligonucleotides retains the stability of DNA duplexes. The duplex structures were studied by molecular modelling which support the results of melting experiments. (C) 2008 Elsevier Ltd. All rights reserved.
ISSN: 09680896
DOI: 10.1016/j.bmc.2008.08.026

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