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Expanding the Horizon of the Thymine Isostere Biochemistry: Unique Cyclobutane Dimers Formed by Photoreaction between a Thymine and a Toluene Residue in the Dinucleotide Framework
Author(s) -
Liu Degang,
Zhou Yan,
Pu Jingzhi,
Li Lei
Publication year - 2012
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.201200816
Subject(s) - thymine , pyrimidine dimer , chemistry , moiety , cyclobutane , residue (chemistry) , stereochemistry , pyrimidine , photochemistry , dna , photolyase , nucleobase , organic chemistry , ring (chemistry) , dna damage , dna repair , biochemistry
Substituted toluenyl groups are considered as close isosteres of the thymine residue. They can be recognized by DNA polymerases as if they were thymine. These toluene derivatives are generally inert toward radical additions, including the [2+2] photo‐cycloadditions, due to the stable structure of the aromatic ring and are usually used as solvents for radical reactions. Surprisingly, after incorporating toluene into the dinucleotide framework, we found that the UV excited thymine residue readily dimerizes with the toluenyl moiety through a [2+2] photo‐addition reaction. Furthermore, the reaction site on the toluenyl moiety is not the C5C6 bond, as commonly observed in cyclobutane pyrimidine dimers, but the C4C5 or C3C4 instead. Such a reaction pattern suggests that in the stacked structure, it is one of these bonds, not the C5C6, that is close to the thymine C5C6 bond. A similar structural feature is found in DNA duplex with a thymine replaced by a 2,4‐difluorotoluene. Our results argue that although the substituted toluenyl moieties closely mimic the size and shape of the thymine residue, their more hydrophobic nature determines that they stack on DNA bases differently from the natural thymine residue and likely cause local conformational changes in duplex DNA.