Products Generated by Amine-Catalyzed Strand Cleavage at Apurinic/Apyrimidinic Sites in DNA: New Insights from a Biomimetic Nucleoside Model System

• DOI: 10.1021/acs.chemrestox.1c00408
• Publication Date: 2022-02-06T13:00:26Z
• Authors: Jay S. Jha; Christopher Nel; Tuhin Haldar; Daniel Peters; Kurt Housh; Kent S. Gates
• Keywords: Deoxyribose; Iminium; Cleavage (geology)

Abasic sites are common in cellular and synthetic DNA. As a result, it is important to characterize the chemical fate of these lesions. Amine-catalyzed strand cleavage at abasic DNA an process which conversion small amounts ring-opened aldehyde residue iminium ion facilitates β-elimination 3'-phosphoryl group. This reaction generates trans-α,β-unsaturated on 3'-terminus break as obligate intermediate. The canonical product expected from amine-catalyzed AP site corresponding sugar remnant resulting hydrolysis this ion. Interestingly, handful studies have reported noncanonical 3'-sugar remnants generated by cleavage, but formation properties products not well-understood. To address knowledge gap, nucleoside system was developed that enabled characterization 2-deoxyribose system. results predict under physiological conditions has potential reversibly generate including cis-alkenal, 3-thio-2,3-dideoxyribose, groups alongside trans-alkenal break. Thus, model reactions provide evidence may be more complex commonly thought, with intermediates residing hub interconverting mixtures. expand list possible arising must chemically or enzymatically removed for completion base excision repair single-strand cells.