Synthesis of N6-dA Damaged DNAs to Probe the Replication Ability of Human Translesion Polymerases

J Org Chem. 2025 Jan 3. doi: 10.1021/acs.joc.4c01683. Online ahead of print.

Abstract

The DNA adducts formed by the alkenylbenzene natural products, safrole (SF) and methyleugenol (MEG) are primarily attributed to their reported carcinogenic properties. Herein, we report a concise strategy to access N6-Ac-SF/MEG-dA phosphoramidites, which were selectively incorporated into DNA oligonucleotides by solid-phase DNA synthesis. The replication studies using human polymerases hpolκ and hpolη showed that both polymerases replicate these adducts error-free, which indicates that these polymerases do not contribute to the adduct-induced mutagenicity.