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.
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.
Christov
Plamen P
PP
Department of Chemistr, Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37235-1822, USA.
Brown
Kyle L
KL
Kozekov
Ivan D
ID
Stone
Michael P
MP
Harris
Thomas M
TM
Rizzo
Carmelo J
CJ
D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D003849:Deoxyguanosine / Q000138:chemical synthesis* / Q000737:chemistry; D005559:Formamides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D005559:Formamides; C475814:N4-(2-deoxypentofuranosyl)-4,6-diamino-5-formamidopyrimidine; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D011743:Pyrimidines; C434331:phosphoramidite; D003849:Deoxyguanosine