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Synthesis of Oligonucleotides Containing the N 6 ‐(2‐Deoxy‐α,β‐ d ‐erythropentofuranosyl)‐2,6‐diamino‐4‐hydroxy‐5‐formamidopyrimidine (Fapy⋅dG) Oxidative Damage Product Derived from 2′‐Deoxyguanosine
Author(s) -
Yang Haozhe,
Tang Joel A.,
Greenberg Marc M.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905795
Subject(s) - oligonucleotide , deoxyguanosine , chemistry , dna oxidation , dna damage , dna , biochemistry
N 6 ‐(2‐Deoxy‐α,β‐ d ‐erythropentofuranosyl)‐2,6‐diamino‐4‐hydroxy‐5‐formamidopyrimidine (Fapy⋅dG) is a major DNA lesion produced from 2′‐deoxyguanosine under oxidizing conditions. Fapy ⋅ dG is produced from a common intermediate that leads to 7,8‐dihydro‐8‐oxo‐2′‐deoxyguanosine (8‐OxodGuo), and in greater quantities in cells. The impact of Fapy ⋅ dG on DNA structure and function is much less well understood than that of 8‐OxodGuo. This is largely due to the significantly greater difficulty in synthesizing oligonucleotides containing Fapy ⋅ dG than 8‐OxodGuo. We describe a synthetic approach for preparing oligonucleotides containing Fapy ⋅ dG that will facilitate intensive studies of this lesion in DNA. A variety of oligonucleotides as long as 30 nucleotides are synthesized. We anticipate that the chemistry described herein will provide an impetus for a wide range of studies involving Fapy ⋅ dG.