title: Oligonucleotide probes containing pyrimidine analogs reveal diminished hydrogen bonding capacity of the DNA adduct O⁶-methyl-G in DNA duplexes.
abstract: Oligonucleotide hybridization probes containing nucleoside analogs offer a potential strategy for binding specific DNA sequences that bear pro-mutagenic O(6)-G alkylation adducts. To optimize O(6)-Me-G-targeting probes, an understanding of how base pairs with O(6)-Me-G are stabilized is needed. In this study, we compared the ability of O(6)-Me-G and G to hydrogen bond with three pyrimidine-like nucleobases (Z, 4-thio-U, and 3-deaza-C) bearing varied hydrogen bond donor and acceptor groups. We found that duplexes containing the pyrimidine analog nucleoside:G pairs were more thermodynamically stable than those containing pyrimidine analog nucleoside:O(6)-alkyl-G pairs. Thus, hydrogen bonding alone was not sufficient to impart selectivity to probes that target O(6)-G alkylation adducts in DNA.
authors: Department of Health Science and Technology, Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 9, 8092 Zurich, Switzerland.
authors: Todor
authors: T
authors: Angelov
authors: Heidi A
authors: HA
authors: Dahlmann
authors: Shana J
authors: SJ
authors: Sturla
mesh_terms: D004247:DNA / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D006860:Hydrogen Bonding; D015345:Oligonucleotide Probes / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D018736:DNA Adducts; D015345:Oligonucleotide Probes; D009841:Oligonucleotides; D011743:Pyrimidines; D004247:DNA
keywords: DNA adduct; Nucleoside analog; Oligonucleotide binding