Oligonucleotides containing 6-aza-2 `-deoxyuridine: Synthesis, nucleobase protection, pH-dependent duplex stability, and metal-DNA formation

Autor(en): Seela, Frank
Chittepu, Padmaja
Stichwörter: 2'-DEOXY-6-AZAURIDINE; 6-AZAURIDINE; BASE-PAIR STABILITY; Chemistry; Chemistry, Organic; CONFORMATION; GENERAL SYNTHESIS; MOLECULAR WIRE; PHOSPHORAMIDITES; PYRIMIDINE NUCLEOSIDES; URACIL; URIDINE DERIVATIVES
Erscheinungsdatum: 2007
Herausgeber: AMER CHEMICAL SOC
Journal: JOURNAL OF ORGANIC CHEMISTRY
Volumen: 72
Ausgabe: 12
Startseite: 4358
Seitenende: 4366
Zusammenfassung: 
Oligodeoxyribonucleotides containing the nucleoside 6-aza-2'-deoxyuridine z(6)U(d) (1a) were prepared by using solid-phase synthesis. As the pK(a) value of this nucleoside is 6.8, unwanted side reactions are observed. Consequently, nitrogen-3 was protected (o-anisoyl protection). The phosphoramidite of 1a prepared on this route was as efficient as the building blocks of canonical nucleosides in allowing multiple incorporations into oligonucleotides. Oligonucleotide duplexes containing 1a show a pH dependence of the T-m value. This is caused by nucleobase deprotonation occurring on compound 1a already under neutral conditions. Metal (M)-DNA formation was studied in the presence of Zn+2 ions. It is demonstrated that 6-azauracil-modified duplexes form M-DNA already in neutral medium while alkaline conditions (above pH 8.5) are required for natural DNA. The conformational analysis of the sugar moiety of the nucleoside 1a and its anisoyl derivative 5a shows a preferred N-conformation in solution while an S-conformation for compound 1a was obtained in the solid state (single-crystal X-ray analysis).
ISSN: 00223263
DOI: 10.1021/jo0702903

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