Structural study of the N6-(Deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamido-pyrimidine DNA adduct

Abstract

N6-(Deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine (MeFapy-dG) is the methylated and persistent ring opened product of the common N7 alkylation site of guanines in DNA, formed upon the subsequent addition of hydroxide to C8. Depending on the sequence, MeFapy-dG has been shown to block DNA polymerases and cause both transversion and deletion mutations during replication. It is an important adduct to study due to its persistence and mutagenicity, but has not been looked into extensively because of the lack of synthetic availability. Recently, Professor Carmelo J. Rizzo and co-workers at Vanderbilt University developed a novel synthetic method for the incorporation of the MeFapy-dG adduct into oligonucleotides, which allowed examination of potential conformations and anomers of the MeFapy-dG adduct within a particular oligonucleotide sequence via nuclear magnetic resonance spectroscopy.