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Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry

The clinically widely-used anticancer drug, cisplatin, binds strongly to DNA as a DNA-damaging agent. Herein, we investigated the interaction of cisplatin with a 15-mer single-stranded C,T-rich oligodeoxynucleotide, 5′-CCTT(4)CTT(7)G(8)C(9)T(10)TCTCC-3′ (ODN15), using ultra-high resolution Fourier t...

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Autores principales: Zeng, Wenjuan, Zhang, Yanyan, Zheng, Wei, Luo, Qun, Han, Juanjuan, Liu, Jian’an, Zhao, Yao, Jia, Feifei, Wu, Kui, Wang, Fuyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571787/
https://www.ncbi.nlm.nih.gov/pubmed/31091778
http://dx.doi.org/10.3390/molecules24101852
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author Zeng, Wenjuan
Zhang, Yanyan
Zheng, Wei
Luo, Qun
Han, Juanjuan
Liu, Jian’an
Zhao, Yao
Jia, Feifei
Wu, Kui
Wang, Fuyi
author_facet Zeng, Wenjuan
Zhang, Yanyan
Zheng, Wei
Luo, Qun
Han, Juanjuan
Liu, Jian’an
Zhao, Yao
Jia, Feifei
Wu, Kui
Wang, Fuyi
author_sort Zeng, Wenjuan
collection PubMed
description The clinically widely-used anticancer drug, cisplatin, binds strongly to DNA as a DNA-damaging agent. Herein, we investigated the interaction of cisplatin with a 15-mer single-stranded C,T-rich oligodeoxynucleotide, 5′-CCTT(4)CTT(7)G(8)C(9)T(10)TCTCC-3′ (ODN15), using ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) in conjunction with tandem mass spectrometry (top-down MS). Top-down MS analysis with collision-induced dissociation (CID) fragmentation of the mono-platinated and di-platinated ODN15 provided abundant and informative Pt-containing or Pt-free a/[a − B], w and internal fragments, allowing the unambiguous identification of T(4), T(7), C(9), and T(10) as the platination sites on the cisplatin-ODN15 adducts. These results revealed that, in addition to the well-established guanine site, the unexpected thermodynamic binding of cisplatin to cytosine and thymine bases was also evident at the oligonucleotide level. Furthermore, the binding models of cisplatin with cytosine and thymine bases were built as the Pt coordinated to cytosine-N(3) and thymine-N(3) with displacement of the proton or tautomerization of thymine. These findings contribute to a better understanding of the mechanism of action of cisplatin and its preference for gene loci when the drug binds to cellular DNA, and also demonstrate the great potential and superiority of FT-ICR MS in studying the interactions of metallodrugs with large biomolecules.
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spelling pubmed-65717872019-06-18 Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry Zeng, Wenjuan Zhang, Yanyan Zheng, Wei Luo, Qun Han, Juanjuan Liu, Jian’an Zhao, Yao Jia, Feifei Wu, Kui Wang, Fuyi Molecules Article The clinically widely-used anticancer drug, cisplatin, binds strongly to DNA as a DNA-damaging agent. Herein, we investigated the interaction of cisplatin with a 15-mer single-stranded C,T-rich oligodeoxynucleotide, 5′-CCTT(4)CTT(7)G(8)C(9)T(10)TCTCC-3′ (ODN15), using ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) in conjunction with tandem mass spectrometry (top-down MS). Top-down MS analysis with collision-induced dissociation (CID) fragmentation of the mono-platinated and di-platinated ODN15 provided abundant and informative Pt-containing or Pt-free a/[a − B], w and internal fragments, allowing the unambiguous identification of T(4), T(7), C(9), and T(10) as the platination sites on the cisplatin-ODN15 adducts. These results revealed that, in addition to the well-established guanine site, the unexpected thermodynamic binding of cisplatin to cytosine and thymine bases was also evident at the oligonucleotide level. Furthermore, the binding models of cisplatin with cytosine and thymine bases were built as the Pt coordinated to cytosine-N(3) and thymine-N(3) with displacement of the proton or tautomerization of thymine. These findings contribute to a better understanding of the mechanism of action of cisplatin and its preference for gene loci when the drug binds to cellular DNA, and also demonstrate the great potential and superiority of FT-ICR MS in studying the interactions of metallodrugs with large biomolecules. MDPI 2019-05-14 /pmc/articles/PMC6571787/ /pubmed/31091778 http://dx.doi.org/10.3390/molecules24101852 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zeng, Wenjuan
Zhang, Yanyan
Zheng, Wei
Luo, Qun
Han, Juanjuan
Liu, Jian’an
Zhao, Yao
Jia, Feifei
Wu, Kui
Wang, Fuyi
Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry
title Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry
title_full Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry
title_fullStr Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry
title_full_unstemmed Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry
title_short Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry
title_sort discovery of cisplatin binding to thymine and cytosine on a single-stranded oligodeoxynucleotide by high resolution ft-icr mass spectrometry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571787/
https://www.ncbi.nlm.nih.gov/pubmed/31091778
http://dx.doi.org/10.3390/molecules24101852
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