Pyrrolo-dC oligonucleotides bearing alkynyl side chains with terminal triple bonds: synthesis, base pairing and fluorescent dye conjugates prepared by the azide-alkyne ``click'' reaction
Autor(en): | Seela, Frank Sirivolu, Venkata Ramana |
Stichwörter: | 1,3-DIPOLAR CYCLOADDITION REACTION; 2'-DEOXYCYTIDINE; 3,N-4-ETHENO; Chemistry; Chemistry, Organic; COUMARIN; DNA; FUNCTIONALIZATION; NUCLEOSIDE ANALOGS; PROBE; ZOSTER-VIRUS VZV | Erscheinungsdatum: | 2008 | Herausgeber: | ROYAL SOC CHEMISTRY | Journal: | ORGANIC & BIOMOLECULAR CHEMISTRY | Volumen: | 6 | Ausgabe: | 9 | Startseite: | 1674 | Seitenende: | 1687 | Zusammenfassung: | 5-(Octa-1,7-diynyl)-2'-deoxyuridine was converted into the furano-dU derivative 7 by copper-catalyzed cyclization; the pyrolodC-derivative 3 was formed upon ammonolysis. The bicyclic nucleosides 3 and 7 as well as the corresponding non-cyclic precursors 4 and 6 all containing terminal C C bonds were conjugated with the non-fluorescent 3-azido-7-hydroxycoumarin 5 employing the copper(I)-catalyzed Huisgen-Sharpless-Meldal cycloaddition ``click reaction''. Strongly fluorescent 1H-1,2,3-triazole conjugates (30-33) are formed incorporating two fluorescent reporters-the pyrdC nucleoside and the coumarin moiety. Oligonucleotides incorporating 6-alkynyl and 6-alkyl 7H-pyrrolo[2,3-d] pyrimidin-2(3H)-one nucleosides (3 and 2f) have been prepared by solid-phase synthesis using the phosphoramidite building blocks 10 and 13; the pyrrolo-dC oligonucleotides are formed during ammonia treatment. The duplex stability of oligonucleotides containing 3 and related derivatives was studied. Oligonucleotides with terminal triple bonded nucleosides such as 3 are more stabilizing than those lacking a side chain with terminal unsaturation; open-chain derivatives (4) are even more efficient. The click reaction was also performed on oligonucleotides containing the pyrdC-derivative 3 and the fluorescence properties of nucleosides, oligonucleotides and their coumarin conjugates were studied. |
ISSN: | 14770520 | DOI: | 10.1039/b719459e |
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