DNA with Branched Internal Side Chains: Synthesis of 5-Tripropargylamine-dU and Conjugation by an Azide-Alkyne Double Click Reaction

Autor(en): Sirivolu, Venkata Ramana
Chittepu, Padmaja
Seela, Frank
Stichwörter: BASE-PAIR STABILITY; Biochemistry & Molecular Biology; branched DNA; CHEMISTRY; Chemistry, Medicinal; click chemistry; CYCLOADDITION; DUPLEX STABILITY; fluorescence; FUNCTIONALIZATION; MAJOR-GROOVE; nucleosides; OLIGONUCLEOTIDES; Pharmacology & Pharmacy; PYRIMIDINES; SUBSTITUENTS; TERMINAL TRIPLE BONDS
Erscheinungsdatum: 2008
Herausgeber: WILEY-V C H VERLAG GMBH
Journal: CHEMBIOCHEM
Volumen: 9
Ausgabe: 14
Startseite: 2305
Seitenende: 2316
Zusammenfassung: 
5-Tripropargylamine-2'-deoxyuridine (1a) containing two terminal triple bonds was synthesized by a Pd-assisted Sonogashira cross-coupling reaction and was subsequently converted into the corresponding phosphoramidite building block (9) and employed in solid-phase oligonucleotide synthesis. T-m experiments demonstrated that the presence of covalently attached branched tripropargylamine residues has a positive effect on the base pair stability. The two terminal C C bonds of modified DNA were function alized by means of Cu-1-mediated 1,3-dipolar cycloaddition reactions (click chemistry) with azides such as 3-azido-7-hydroxycoumarin or 3-azido-3'- deoxythymidine (AZT) both in solution and on solid support in particular, with the nonfluorescent nonfluorescent 3-azido-7-hydroxycoumarin a strongly fluorescent oligonucleotide bis-dye conjugate was generated. For comparison, the N(3)-propargylated 2-deoxyuridine 2 was prepared from 2'-deoxyuridine and propargyl bromide and incorporated into DNA. The two terminal pargylamine triple bonds of 1a allow the simultaneous post-modification of DNA by two reporter molecules and can be applied to almost any azido derivatives (oligonucleotides, proteins, polysaccharides etc.) including those forming dendrimeric side chains.
ISSN: 14394227
DOI: 10.1002/cbic.200800313

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