Advanced

The polyamines spermidine and spermine retard the platination rate of single-stranded DNA oligomers and plasmid

Sykfont Snygg, Åse LU ; Hung, Melling and Elmroth, Sofi LU (2007) In Journal of Inorganic Biochemistry 101(8). p.1153-1164
Abstract
The presence of polyamines in living cells is crucial for survival. Due to their high net charge at physiological pH, polyamines effectively charge neutralize the phosphodiester backbone of DNA in an interaction that also may protect the DNA from external damage. We here present a study illustrating the influence of spermidine and spermine on the platination reactions of the model oligonucleotides d(T(6)GT(6)), d(T(12)GT(12)), and d(T(24)GT(24)), and the pUC18 DNA plasmid. The aquated forms of the anticancer active compounds cisplatin (cis-[Pt(NH3,)(2)Cl-2]) and the major Pt(II) metabolite of JM216 (Cis-[PtCl2(NH3)(C-C6H11 NH2)], JM118) were used as platination reagents. The study shows that the kinetics for formation of the coordinative... (More)
The presence of polyamines in living cells is crucial for survival. Due to their high net charge at physiological pH, polyamines effectively charge neutralize the phosphodiester backbone of DNA in an interaction that also may protect the DNA from external damage. We here present a study illustrating the influence of spermidine and spermine on the platination reactions of the model oligonucleotides d(T(6)GT(6)), d(T(12)GT(12)), and d(T(24)GT(24)), and the pUC18 DNA plasmid. The aquated forms of the anticancer active compounds cisplatin (cis-[Pt(NH3,)(2)Cl-2]) and the major Pt(II) metabolite of JM216 (Cis-[PtCl2(NH3)(C-C6H11 NH2)], JM118) were used as platination reagents. The study shows that the kinetics for formation of the coordinative Pt-DNA adduct are strongly influenced by the presence of sub-millimolar polyamine concentrations. At polyamine concentrations in the mu M-range, the reactions remain salt-dependent. In contrast, platination of pUC 18 is effectively prevented at mM concentrations of both spermidine and spermine with the latter as the more potent inhibitor. The results suggest that variations of intracellular polyamine concentrations may have a profound influence on the efficacy by which cationically charged reagents interfere with DNA function in vivo by modulation of the preassociation conditions. (c) 2007 Elsevier Inc. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
platinum, acid, nucleic, spermidine, spermine, DNA damage, toxicity, anticancer drug
in
Journal of Inorganic Biochemistry
volume
101
issue
8
pages
1153 - 1164
publisher
Elsevier
external identifiers
  • wos:000248775400007
  • scopus:34347404076
ISSN
1873-3344
DOI
10.1016/j.jinorgbio.2007.04.017
language
English
LU publication?
yes
id
59c3718b-eeb3-4694-9c82-36928bb783ef (old id 691699)
date added to LUP
2007-12-19 08:47:26
date last changed
2017-01-01 07:13:12
@article{59c3718b-eeb3-4694-9c82-36928bb783ef,
  abstract     = {The presence of polyamines in living cells is crucial for survival. Due to their high net charge at physiological pH, polyamines effectively charge neutralize the phosphodiester backbone of DNA in an interaction that also may protect the DNA from external damage. We here present a study illustrating the influence of spermidine and spermine on the platination reactions of the model oligonucleotides d(T(6)GT(6)), d(T(12)GT(12)), and d(T(24)GT(24)), and the pUC18 DNA plasmid. The aquated forms of the anticancer active compounds cisplatin (cis-[Pt(NH3,)(2)Cl-2]) and the major Pt(II) metabolite of JM216 (Cis-[PtCl2(NH3)(C-C6H11 NH2)], JM118) were used as platination reagents. The study shows that the kinetics for formation of the coordinative Pt-DNA adduct are strongly influenced by the presence of sub-millimolar polyamine concentrations. At polyamine concentrations in the mu M-range, the reactions remain salt-dependent. In contrast, platination of pUC 18 is effectively prevented at mM concentrations of both spermidine and spermine with the latter as the more potent inhibitor. The results suggest that variations of intracellular polyamine concentrations may have a profound influence on the efficacy by which cationically charged reagents interfere with DNA function in vivo by modulation of the preassociation conditions. (c) 2007 Elsevier Inc. All rights reserved.},
  author       = {Sykfont Snygg, Åse and Hung, Melling and Elmroth, Sofi},
  issn         = {1873-3344},
  keyword      = {platinum,acid,nucleic,spermidine,spermine,DNA damage,toxicity,anticancer drug},
  language     = {eng},
  number       = {8},
  pages        = {1153--1164},
  publisher    = {Elsevier},
  series       = {Journal of Inorganic Biochemistry},
  title        = {The polyamines spermidine and spermine retard the platination rate of single-stranded DNA oligomers and plasmid},
  url          = {http://dx.doi.org/10.1016/j.jinorgbio.2007.04.017},
  volume       = {101},
  year         = {2007},
}