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Comparison of Cis- and Oxaliplatin-induced Destabilization of 15-mer DNA- and RNA Duplexes by Binding to Centrally Located GG- and GNG Sequences

Polonyi, Christopher LU ; Albertsson, Ingrid; Damian, Mariana LU and Elmroth, Sofi LU (2013) In Zeitschrift für Anorganische und Allgemeine Chemie 639(8-9). p.1655-1660
Abstract
Thermodynamic parameters are presented here illustrating the effects caused by the two anticancer active metal complexes cisplatin and oxaliplatin after introduction into four closely related RNA and DNA duplexes. The duplexes used are blunt end, fully complementary 15-mer duplexes with a centrally located either GG- or GNG (here: N = T or U) binding site. For all duplexes, a common trend of reduced melting temperature was observed after platination. Analysis of the thermodynamic parameters for the duplex dissociation reactions showed good correlation between variations in melting temperatures (T-m) and ground state enthalpies (Delta H) in both DNA- and RNA duplexes. The melting temperatures of the native duplexes were found to be... (More)
Thermodynamic parameters are presented here illustrating the effects caused by the two anticancer active metal complexes cisplatin and oxaliplatin after introduction into four closely related RNA and DNA duplexes. The duplexes used are blunt end, fully complementary 15-mer duplexes with a centrally located either GG- or GNG (here: N = T or U) binding site. For all duplexes, a common trend of reduced melting temperature was observed after platination. Analysis of the thermodynamic parameters for the duplex dissociation reactions showed good correlation between variations in melting temperatures (T-m) and ground state enthalpies (Delta H) in both DNA- and RNA duplexes. The melting temperatures of the native duplexes were found to be determined by their chemical nature, i.e. with observed T-m -values of ca. 50 degrees C for DNA and ca. 61 degrees C for RNA (C-T = 2 mu M and CNa+ = 129 mM, pH 6.3). Of the two types of nucleic acids, RNA is the one that exhibits the most pronounced sensitivity towards introduction of the platinum complexes, and with oxaliplatin as the more influential metalation reagent. Of note is that the thermal destabilization caused by oxaliplatin interacting with a centrally located GUG-sequence results in a duplex stability below native DNA. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cisplatin, Oxaliplatin, DNA, RNA, Duplex melting
in
Zeitschrift für Anorganische und Allgemeine Chemie
volume
639
issue
8-9
pages
1655 - 1660
publisher
Wiley-Blackwell
external identifiers
  • wos:000330180900047
  • scopus:84880555537
ISSN
0044-2313
DOI
10.1002/zaac.201300060
language
English
LU publication?
yes
id
39de26b7-6b07-407e-a605-6447f98b0f30 (old id 4318811)
date added to LUP
2014-02-25 12:50:08
date last changed
2019-02-20 05:27:44
@article{39de26b7-6b07-407e-a605-6447f98b0f30,
  abstract     = {Thermodynamic parameters are presented here illustrating the effects caused by the two anticancer active metal complexes cisplatin and oxaliplatin after introduction into four closely related RNA and DNA duplexes. The duplexes used are blunt end, fully complementary 15-mer duplexes with a centrally located either GG- or GNG (here: N = T or U) binding site. For all duplexes, a common trend of reduced melting temperature was observed after platination. Analysis of the thermodynamic parameters for the duplex dissociation reactions showed good correlation between variations in melting temperatures (T-m) and ground state enthalpies (Delta H) in both DNA- and RNA duplexes. The melting temperatures of the native duplexes were found to be determined by their chemical nature, i.e. with observed T-m -values of ca. 50 degrees C for DNA and ca. 61 degrees C for RNA (C-T = 2 mu M and CNa+ = 129 mM, pH 6.3). Of the two types of nucleic acids, RNA is the one that exhibits the most pronounced sensitivity towards introduction of the platinum complexes, and with oxaliplatin as the more influential metalation reagent. Of note is that the thermal destabilization caused by oxaliplatin interacting with a centrally located GUG-sequence results in a duplex stability below native DNA.},
  author       = {Polonyi, Christopher and Albertsson, Ingrid and Damian, Mariana and Elmroth, Sofi},
  issn         = {0044-2313},
  keyword      = {Cisplatin,Oxaliplatin,DNA,RNA,Duplex melting},
  language     = {eng},
  number       = {8-9},
  pages        = {1655--1660},
  publisher    = {Wiley-Blackwell},
  series       = {Zeitschrift für Anorganische und Allgemeine Chemie},
  title        = {Comparison of Cis- and Oxaliplatin-induced Destabilization of 15-mer DNA- and RNA Duplexes by Binding to Centrally Located GG- and GNG Sequences},
  url          = {http://dx.doi.org/10.1002/zaac.201300060},
  volume       = {639},
  year         = {2013},
}