A new water soluble copper N-heterocyclic carbene complex delivers mild O(6)G-selective RNA alkylation

作者:Rasale Dnyaneshwar; Patil Kiran; Sauter Basilius; Geigle Stefanie; Zhanybekova Saute; Gillingham Dennis*
来源:Chemical Communications, 2018, 54(66): 9174-9177.
DOI:10.1039/c8cc04476g

摘要

We show here that copper carbenes generated from diazo acetamides alkylate single RNAs, mRNAs, or pools of total transcriptome RNA, delivering exclusively alkylation at the O-6 position in guanine (O(6)G). Although the reaction is effective with free copper some RNA fragmentation occurs, a problem we resolve by developing a novel water-stable copper N-heterocyclic carbene complex. Carboxymethyl adducts at O(6)G are known mutagenic lesions in DNA but their relevance in RNA biochemistry is unknown. As a case-in-point we re-examine an old controversy regarding whether O(6)G damage in RNA is susceptible to direct RNA repair.

  • 出版日期2018-8-25