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

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1852 ◽  
Author(s):  
Wenjuan Zeng ◽  
Yanyan Zhang ◽  
Wei Zheng ◽  
Qun Luo ◽  
Juanjuan Han ◽  
...  

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′-CCTT4CTT7G8C9T10TCTCC-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 T4, T7, C9, and T10 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.

2019 ◽  
Vol 52 ◽  
pp. 1-8 ◽  
Author(s):  
Virginia Echavarri-Bravo ◽  
Matthias Tinzl ◽  
Will Kew ◽  
Faye Cruickshank ◽  
C. Logan Mackay ◽  
...  

2019 ◽  
Author(s):  
Min Cui ◽  
Cheng Li ◽  
Yingjun Chen ◽  
Fan Zhang ◽  
Jun Li ◽  
...  

Abstract. The molecular composition and structure of polar organic matters (POM) in particles emitted from various vessels and excavators were characterized using Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). POM was extracted by purified water and was discussed by elemental composition which was divided into three groups, namely CHO, CHON and S-containing compounds (CHONS and CHOS). The results showed that: (i) CHO (accounting for 49 % of total POM relative peak response) was the most abundant group for all tested off-road engines, followed by CHON (33 %) and CHOS (35 %) for diesel- and HFO (heavy fuel oil)-fueled off-road equipment, respectively. (ii) The abundance and structure of the CHON group in water extracts were different in terms of engine type and load. The fraction of relative peak response of CHON was highest for excavator emissions under the working mode compared to other modes (idling and moving). Furthermore, dinitrophenol and methyl dinitrophenol were the most abundant emission species for excavators with high rated speed, while nitronaphthol and methyl nitronaphthol were more important for low rated speed vessels. (iii) The composition and structure of S-containing compounds was directly influenced by fuel oil characteristics (sulfur content and aromatic ring), with much more condensed aromatic rings in S-containing compounds observed for HFO-fueled vessels, while more abundant aliphatic chains were observed in emissions from diesel equipment. Overall, higher fractions of condensed hydrocarbons and aromatic rings in POM emitted from vessels using HFO caused strong optical absorption capacity. And different structures existing in POM could provide a direction to qualitative and quantities the exact organic compounds as tracers to distinguish the emission from diesel or HFO- fueled off-road engines.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Angelica Bianco ◽  
Laurent Deguillaume ◽  
Nadine Chaumerliac ◽  
Mickaël Vaïtilingom ◽  
Miao Wang ◽  
...  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


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