Fluorescent Nucleobase Analogues with Extended Pi Surfaces Stabilize DNA Duplexes Containing O6‐Alkylguanine Adducts

Chemical alkylation of DNA produces potentially toxic and mutagenic damage such as O6‐alkylguanine (O6‐alkylG) adducts. Non‐natural nucleoside analogues that pair with DNA adducts provide a potential basis for studying damaged DNA. Herein, we evaluated the base pairing properties of elongated nucleo...

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Bibliographic Details
Published in:Helvetica chimica acta 2018-07, Vol.101 (7), p.n/a
Main Authors: Dahlmann, Heidi A., Berger, Florence D., Kung, Ryan W., Wyss, Laura A., Gubler, Irina, McKeague, Maureen, Wetmore, Stacey D., Sturla, Shana J.
Format: Article
Language:English
Subjects:
Adducts
Alkylation
Analogs
Antiretroviral drugs
Base pairs
Bases (nucleic acids)
Damage assessment
Deoxyribonucleic acid
DNA
DNA adducts
DNA damage
DNA probes
DNA recognition
Elongation
Fluorescence
fluorescent probes
Hybridization
Hydrophobicity
nucleobase analogues
Nucleoside analogs
Nucleosides
Organic chemistry
Probes
Retirement
stacking interactions
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Summary:Chemical alkylation of DNA produces potentially toxic and mutagenic damage such as O6‐alkylguanine (O6‐alkylG) adducts. Non‐natural nucleoside analogues that pair with DNA adducts provide a potential basis for studying damaged DNA. Herein, we evaluated the base pairing properties of elongated nucleoside analogues containing napthalene‐derived tricyclic nucleobases as DNA adduct‐pairing nucleoside analogues in DNA hybridization probes. DNA duplex melting studies revealed that the elongated nucleoside analogs formed more stable base pairs opposite O6‐alkylG than G and were better able to distinguish between G, O6‐alkylG, and an abasic site than any previously described nucleoside analogue. DNA duplexes containing an elongated base analogue exhibited different fluorescence intensities when paired opposite O6‐alkylG vs. G or abasic sites. Their selectivity for stabilizing alkylated DNA make the elongated hydrophobic base analogues improved candidates for incorporating into DNA hybridization probes targeting O6‐alkylG.
ISSN:0018-019X
1522-2675
DOI:10.1002/hlca.201800066