Department of Chemistry, University of Utah, 315 S. 1400 E., Salt Lake City, Utah 84112-0850, United States.
J Org Chem. 2022 Sep 2;87(17):11865-11870. doi: 10.1021/acs.joc.2c01371. Epub 2022 Aug 12.
Exposure of DNA to oxidants results in modification of the electron-rich guanine heterocycle including formation of the mutagenic 5-carboxamido-5-formamido-2-iminohydantoin (2Ih) lesion. Previously thought to exist solely as a pair of diastereomers, we found under biologically relevant conditions that 2Ih reversibly closes to a formerly hypothetical intermediate and opens into a newly discovered regioisomer. In a nucleoside model, only ∼80% of 2Ih existed as the structure studied over the last 20 years with significant isomeric products persisting in buffered aqueous solution.
DNA 暴露于氧化剂会导致富含电子的鸟嘌呤杂环发生修饰，包括形成致突变的 5-羧酰胺基-5-甲酰胺基-2-亚氨基海因（2Ih）损伤。以前认为它仅以一对非对映异构体的形式存在，但是我们在生物相关条件下发现，2Ih 可逆地闭合到以前假设的中间体，并打开形成新发现的区域异构体。在核苷模型中，只有约 80%的 2Ih 存在于过去 20 年研究的结构中，而在缓冲水溶液中仍存在大量的非对映异构体产物。
