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<sub>4</sub>CTT<sub>7</sub>G<sub>8<...
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MDPI AG
2019-05-01
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Online Access: | https://www.mdpi.com/1420-3049/24/10/1852 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wenjuan Zeng Yanyan Zhang Wei Zheng Qun Luo Juanjuan Han Jian’an Liu Yao Zhao Feifei Jia Kui Wu Fuyi Wang |
spellingShingle |
Wenjuan Zeng Yanyan Zhang Wei Zheng Qun Luo Juanjuan Han Jian’an Liu Yao Zhao Feifei Jia Kui Wu Fuyi Wang Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass Spectrometry Molecules cisplatin oligodeoxynucleotide binding sites thymine cytosine FT-ICR MS |
author_facet |
Wenjuan Zeng Yanyan Zhang Wei Zheng Qun Luo Juanjuan Han Jian’an Liu Yao Zhao Feifei Jia Kui Wu Fuyi Wang |
author_sort |
Wenjuan Zeng |
title |
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_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_sort |
discovery of cisplatin binding to thymine and cytosine on a single-stranded oligodeoxynucleotide by high resolution ft-icr mass spectrometry |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2019-05-01 |
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<sub>4</sub>CTT<sub>7</sub>G<sub>8</sub>C<sub>9</sub>T<sub>10</sub>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<sub>4</sub>, T<sub>7</sub>, C<sub>9</sub>, and T<sub>10</sub> 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. |
topic |
cisplatin oligodeoxynucleotide binding sites thymine cytosine FT-ICR MS |
url |
https://www.mdpi.com/1420-3049/24/10/1852 |
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doaj-4d08fd48b125440da84939bd273a00b72020-11-25T02:08:39ZengMDPI AGMolecules1420-30492019-05-012410185210.3390/molecules24101852molecules24101852Discovery of Cisplatin Binding to Thymine and Cytosine on a Single-Stranded Oligodeoxynucleotide by High Resolution FT-ICR Mass SpectrometryWenjuan Zeng0Yanyan Zhang1Wei Zheng2Qun Luo3Juanjuan Han4Jian’an Liu5Yao Zhao6Feifei Jia7Kui Wu8Fuyi Wang9Beijing National Laboratory for Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaBeijing National Laboratory for Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaBeijing National Laboratory for Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaBeijing National Laboratory for Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaBeijing National Laboratory for Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaBeijing National Laboratory for Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaBeijing National Laboratory for Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaBeijing National Laboratory for Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaKey Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, ChinaBeijing National Laboratory for Molecular Sciences, National Centre for Mass Spectrometry in Beijing, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, ChinaThe 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<sub>4</sub>CTT<sub>7</sub>G<sub>8</sub>C<sub>9</sub>T<sub>10</sub>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<sub>4</sub>, T<sub>7</sub>, C<sub>9</sub>, and T<sub>10</sub> 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.https://www.mdpi.com/1420-3049/24/10/1852cisplatinoligodeoxynucleotidebinding sitesthyminecytosineFT-ICR MS |