Guanine and 8-Azaguanine in Anomeric DNA Hybrid Base Pairs: Stability, Fluorescence Sensing, and Efficient Mismatch Discrimination with alpha-D-Nucleosides

Autor(en): Liu, Jiang
Ingale, Sachin A.
Seela, Frank
Stichwörter: 2'-DEOXYRIBONUCLEOSIDES; 8-AZAPURINES; Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry; Chemistry, Multidisciplinary; Chemistry, Organic; DEOXYADENOSINE; DUPLEX; MOLECULAR-MECHANICS; NUCLEIC-ACIDS; NUCLEOTIDES; PARALLEL; SOLID-PHASE SYNTHESIS; STRAND ORIENTATION
Erscheinungsdatum: 2018
Herausgeber: AMER CHEMICAL SOC
Journal: BIOCONJUGATE CHEMISTRY
Volumen: 29
Ausgabe: 7
Startseite: 2265
Seitenende: 2277
Zusammenfassung: 
The alpha-anomers of 8-aza-2'-deoxyguanosine (alpha G(d)*) and 2'-deoxyguanosine (alpha G(d)) were site-specifically incorporated in 12-mer duplexes opposite to the four canonical DNA constituents alpha G(d)*, dG, dT, and dC. Oligodeoxyribonucleotides containing aGd* display significant fluorescence at slightly elevated pH (8.0). Oligodeoxyribonucleotides incorporating beta-anomeric 8-aza-2'-deoxyguanosine (G(d)*) and canonical dG were studied for comparison. For alpha G(d)* synthesis, an efficient purification of anomeric 8-azaguanine nucleosides was developed on the basis of protected intermediates, and a new alpha G(d)* phosphoramidite was prepared. Differences were observed for sugar conformations (N vs S) and pK(a) values of anomeric nucleosides. Duplex stability and mismatch discrimination were studied employing UV-dependent melting and fluorescence quenching. A gradual fluorescence change takes place in duplex DNA when the alpha-nucleoside alpha G(d)* was positioned opposite to the four canonical beta-nucleosides. The strongest fluorescence decrease appeared in duplexes incorporating alpha G(d)*-Cd base pair matches. Decreasing fluorescence corresponds to increasing T-m values. For mismatch discrimination, the alpha-anomers alpha G(d)* and aGd are more efficient than the corresponding beta-nucleosides. Duplexes with single ``purine-purine'' alpha G(d)*-alpha G(d)* or alpha G(d)-alpha G(d) base pairs are significantly more stable than those displaying beta-D configuration. CD spectra indicate that single mutations by alpha-anomeric nucleosides do not affect the global structure of B-DNA.
ISSN: 10431802
DOI: 10.1021/acs.bioconjchem.8b00261

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