Journal article

What are the Potential Sites of DNA Attack by N-Acetyl-p-benzoquinone Imine (NAPQI)?

Siqi Li, Michael G Leeming, Bun Chan, Richard AJ O'Hair

Australian Journal of Chemistry | CSIRO PUBLISHING | Published : 2020

Abstract

Metabolic bioactivation of small molecules can produce electrophilic metabolites that can covalently modify proteins and DNA. Paracetamol (APAP) is a commonly used over-the-counter analgesic, and its hepatotoxic side effects have been postulated to be due to the formation of the electrophilic metabolite N-acetylbenzoquinone imine (NAPQI). It has been established that NAPQI reacts to form covalent bonds to the side-chain functional groups of cysteine, methionine, tyrosine, and tryptophan residues. While there have been scattered reports that APAP can form adducts with DNA the nature of these adducts have not yet been fully characterised. Here the four deoxynucleosides, deoxyguanosine (dG), de..

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Grants

Awarded by RIKEN Information Systems and Cybersecurity (ISC), Japan


Funding Acknowledgements

The authors thank the Bio21 Mass Spectrometry and Proteomics Facility for access to the Agilent 6520 Q-Tof mass spectrometer and the Shimadzu analytical and preparative HPLC. Computer time was provided by the RIKEN Information Systems and Cybersecurity (ISC) (Project Q19266), Japan, and National Computational Infrastructure (NCI), Australia.