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We present a chemical method to selectively tag and enrich thymine modifications, 5-formyluracil (5-fU) and 5-hydroxymethyluracil (5-hmU), found naturally in DNA. Inherent reactivity differences have enabled us to tag 5-fU chemoselectively over its C modification counterpart, 5-formylcytosine (5-fC). We rationalized the enhanced reactivity of 5-fU compared to 5-fC via ab initio quantum mechanical calculations. We exploited this chemical tagging reaction to provide proof of concept for the enrichment of 5-fU containing DNA from a pool that contains 5-fC or no modification. We further demonstrate that 5-hmU can be chemically oxidized to 5-fU, providing a strategy for the enrichment of 5-hmU. These methods will enable the mapping of 5-fU and 5-hmU in genomic DNA, to provide insights into their functional role and dynamics in biology.

Original publication

DOI

10.1021/jacs.5b03730

Type

Journal article

Journal

J Am Chem Soc

Publication Date

29/07/2015

Volume

137

Pages

9270 - 9272

Keywords

Base Sequence, DNA, Models, Molecular, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Pentoxyl, Thymine, Uracil