Advanced

Kinetics and mechanism for platination of thione-containing nucleotides and oligonucleotides: evaluation of the salt dependence

Kjellström, Johan LU and Elmroth, Sofi LU (2003) In Journal of Biological Inorganic Chemistry 8(1-2). p.38-44
Abstract
Reactions of cis-[PtCl(NH3)(CyNH2)(OH2)](+) (Cy = cyclohexyl) with thione-containing single-stranded oligonucleotides d(T8XT8) and d(XT16) (X = I-s6 or U-s4) and the mononucleotides 4-thiouridine ((UMP)-U-s4) and 6-mercaptoinosine ((IMP)-I-s6) have been studied in aqueous solution at pH 4.1. The reaction kinetics was followed using HPLC methodology as a function of ionic strength in the interval 5.0 mM less than or equal to I less than or equal to 300 mM. A two-fold kinetic preference for reaction with the I-s6 moiety over U-s4 is observed in both monomeric and oligomeric systems. The rate for adduct formation with the oligonucleotides d(T8XT8) and d(XT16) decreases with increasing ionic strength of the medium. The effect is most... (More)
Reactions of cis-[PtCl(NH3)(CyNH2)(OH2)](+) (Cy = cyclohexyl) with thione-containing single-stranded oligonucleotides d(T8XT8) and d(XT16) (X = I-s6 or U-s4) and the mononucleotides 4-thiouridine ((UMP)-U-s4) and 6-mercaptoinosine ((IMP)-I-s6) have been studied in aqueous solution at pH 4.1. The reaction kinetics was followed using HPLC methodology as a function of ionic strength in the interval 5.0 mM less than or equal to I less than or equal to 300 mM. A two-fold kinetic preference for reaction with the I-s6 moiety over U-s4 is observed in both monomeric and oligomeric systems. The rate for adduct formation with the oligonucleotides d(T8XT8) and d(XT16) decreases with increasing ionic strength of the medium. The effect is most pronounced for adduct formation with the middle positions, e.g. for d((T8IT8)-I-s6): k(2,app) = 130 M-1 s(-1) and 13 M-1 s(-1) at I = 5.0 and 300 mM, respectively, and slightly less pronounced for adduct formation at the end positions, e.g. for d((IT16)-I-s6): k(2,app) = 130 M-1 s(-1) and 11 M-1 s(-1) at I = 5.0 and 300 mM, respectively. Analysis of the salt dependence using the Bronsted-Debye-Huckel relationship shows that the reactions with the monomers are well described as an interaction between a monovalent cation and a monovalent anion. In contrast, a similar analysis of the oligonucleotide reactions indicates influence from polyelectrolyte effects. The results support a mechanism in which pre-association on the DNA surface precedes adduct formation, regardless of the exact location of the final binding site. (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
4-thiouridine, 6-mercaptoinosine, kinetics, platinum, DNA
in
Journal of Biological Inorganic Chemistry
volume
8
issue
1-2
pages
38 - 44
publisher
Springer
external identifiers
  • wos:000180545000005
  • pmid:12459897
  • scopus:0037254679
ISSN
1432-1327
DOI
language
English
LU publication?
yes
id
289be396-c517-496d-8d0b-30f5d1525776 (old id 319527)
date added to LUP
2007-09-16 09:31:33
date last changed
2018-05-29 10:32:41
@article{289be396-c517-496d-8d0b-30f5d1525776,
  abstract     = {Reactions of cis-[PtCl(NH3)(CyNH2)(OH2)](+) (Cy = cyclohexyl) with thione-containing single-stranded oligonucleotides d(T8XT8) and d(XT16) (X = I-s6 or U-s4) and the mononucleotides 4-thiouridine ((UMP)-U-s4) and 6-mercaptoinosine ((IMP)-I-s6) have been studied in aqueous solution at pH 4.1. The reaction kinetics was followed using HPLC methodology as a function of ionic strength in the interval 5.0 mM less than or equal to I less than or equal to 300 mM. A two-fold kinetic preference for reaction with the I-s6 moiety over U-s4 is observed in both monomeric and oligomeric systems. The rate for adduct formation with the oligonucleotides d(T8XT8) and d(XT16) decreases with increasing ionic strength of the medium. The effect is most pronounced for adduct formation with the middle positions, e.g. for d((T8IT8)-I-s6): k(2,app) = 130 M-1 s(-1) and 13 M-1 s(-1) at I = 5.0 and 300 mM, respectively, and slightly less pronounced for adduct formation at the end positions, e.g. for d((IT16)-I-s6): k(2,app) = 130 M-1 s(-1) and 11 M-1 s(-1) at I = 5.0 and 300 mM, respectively. Analysis of the salt dependence using the Bronsted-Debye-Huckel relationship shows that the reactions with the monomers are well described as an interaction between a monovalent cation and a monovalent anion. In contrast, a similar analysis of the oligonucleotide reactions indicates influence from polyelectrolyte effects. The results support a mechanism in which pre-association on the DNA surface precedes adduct formation, regardless of the exact location of the final binding site.},
  author       = {Kjellström, Johan and Elmroth, Sofi},
  issn         = {1432-1327},
  keyword      = {4-thiouridine,6-mercaptoinosine,kinetics,platinum,DNA},
  language     = {eng},
  number       = {1-2},
  pages        = {38--44},
  publisher    = {Springer},
  series       = {Journal of Biological Inorganic Chemistry},
  title        = {Kinetics and mechanism for platination of thione-containing nucleotides and oligonucleotides: evaluation of the salt dependence},
  url          = {http://dx.doi.org/},
  volume       = {8},
  year         = {2003},
}