Evaluation of DNA adduct damage using G-quadruplex-based DNAzyme

Yi Xiao; Haomin Yi; Jingzhi Zhu; Suhua Chen; Guofang Wang; Yilong Liao; Yuanyuan Lei; Liyin Chen; Xingcai Zhang; Fangfu Ye

doi:10.1016/j.bioactmat.2022.10.002

Evaluation of DNA adduct damage using G-quadruplex-based DNAzyme

Bioact Mater. 2022 Nov 9:23:45-52. doi: 10.1016/j.bioactmat.2022.10.002. eCollection 2023 May.

Authors

Yi Xiao^{1

2

3}, Haomin Yi², Jingzhi Zhu², Suhua Chen⁴, Guofang Wang², Yilong Liao², Yuanyuan Lei², Liyin Chen¹, Xingcai Zhang^{1

5}, Fangfu Ye^{3

6}

Affiliations

¹ School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
² Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, Hunan, China.
³ Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325000, China.
⁴ Hunan Provincial Maternal and Child Health Care Hospital, Changsha, 410008, Hunan, China.
⁵ School of Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁶ Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.

Abstract

Toxicity assessment is a major problem in pharmaceutical candidates and industry chemicals development. However, due to the lack of practical analytical methods for DNA adduct analysis, the safety evaluation of drug and industry chemicals was severely limited. Here, we develop a DNAzyme-based method to detect DNA adduct damage for toxicity assessment of drugs and chemicals. Among 18 structural variants of G4 DNAzyme, EA2 DNAzyme exhibits an obvious DNA damaging effect of styrene oxide (SO) due to its unstable structure. The covalent binding of SO to DNAzyme disrupts the Hoogsteen hydrogen bonding sites of G-plane guanines and affects the formation of the G4 quadruplex. DNA damage chemicals reduce the peroxidase activity of the G4 DNAzyme to monitor the DNA adduct damage by disrupting the structural integrity of the G4 DNAzyme. Our method for genotoxic assessment of pharmaceutical candidates and industrial chemicals can elucidate the complex chemical pathways leading to toxicity, predict toxic effects of chemicals, and evaluate possible risks to human health.

Keywords: DNA adduct Damage; DNAzyme; Pharmaceutical candidates; Styrene oxide; Toxicity assessment.