Site-specific synthesis and characterization of oligonucleotides containing an N6-(2-deoxy-D-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine lesion, the ring-opened product from N7-methylation of deoxyguanosine.

Christov PP, Brown KL, Kozekov ID, Stone MP, Harris TM, Rizzo CJ
Chem Res Toxicol. 2008 21 (12): 2324-33

PMID: 19053322 · PMCID: PMC2701371 · DOI:10.1021/tx800352a

A phosphoramidite reagent of N6-(2-deoxy-D-erythro-pentofuranosyl)-2,6-diamino-1,4-dihydro-4-oxo-5-N-methylformamidopyrimidine (MeFapy-dGuo) lesions was synthesized in four steps from 2'-deoxyguanosine. Fapy nucleosides can rearrange to the pyranose form when the 5'-hydroxyl group is unprotected. The phosphoramidite was incorporated into oligonucleotides using solid-phase synthesis by adjusting the deprotection time for removal of the 5'-dimethoxytrityl group of the MeFapy-dGuo nucleotide, thereby minimizing its rearrangement to the ribopyranose. The furanose and pyranose forms were differentiated by a series of two-dimensional NMR experiments.

MeSH Terms (10)

Chromatography, High Pressure Liquid Deoxyguanosine DNA Damage Formamides Magnetic Resonance Spectroscopy Methylation Oligonucleotides Organophosphorus Compounds Pyrimidines Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

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