Energetics, conformation and recognition of DNA duplexes
modified by methylated analougues of [PtCl(dien)]+

J 2009

Energetics, conformation and recognition of DNA duplexes modified by methylated analougues of [PtCl(dien)]+

NOVÁKOVÁ, Olga, Jaroslav MALINA, Jana KAŠPÁRKOVÁ, Anna HALÁMIKOVÁ, Vladan BERNARD et. al.

Basic information

Original name

Energetics, conformation and recognition of DNA duplexes modified by methylated analougues of [PtCl(dien)]+

Authors

NOVÁKOVÁ, Olga, Jaroslav MALINA, Jana KAŠPÁRKOVÁ, Anna HALÁMIKOVÁ, Vladan BERNARD, Francesco INTINI, Giovanni NATILE and Viktor BRABEC

Edition

Chemistry – A European Journal, Germany, Wiley, 2009, 0947-6539

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10610 Biophysics

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 5.382

Organization unit

Faculty of Science

UT WoS

000267501400018

Keywords (in Czech)

DNA, DNA struktury, platina, polymerizace

Keywords in English

DNA, DNA recognition, DNA structures, platinum, polymerization

Abstract

V originále

In early studies of empirical structure–activity relationships, monodentate PtII complexes were considered to be biologically inactive. Examples of such inactive monodentate PtII compounds are [PtCl (dien)]+ dien=diethylenetriamine) and [PtCl(NH3)3]+. DNA is considered the major biological target of platinum compounds. Thus, monodentate DNA binding of PtII compounds was previously expected to display insignificant biological effects because it was assumed to affect DNA conformation and downstream cellular processes markedly less than the cross-links of bifunctional PtII complexes. More recently it was shown that some monodentate PtII complexes do exhibit biological effects; the active monodentate PtII complexes commonly feature bulkier amine ligands than the hitherto used dien or NH3 groups. We were therefore interested in determining whether a simple but marked enhancement of the bulkiness of the dien ligand in monodentate [Pt (NO3)- (dien)]+ by multiple methylation of this ligand affects the early phases in which platinum compounds exert their biological activity. More specifically, the goals of this study, performed in cell-free media, were to determine how the modification of DNA duplexes by methylated analogues of [Pt (NO3)- (dien)]+ affects their energetics and how the alterations of this biophysical parameter are reflected by the recognition of these duplexes by DNA polymerases and the DNA repair system. We have found that the impact of the methylation of [Pt (NO3) (dien)]+ on the biophysical properties of DNA (thermodynamic, thermal, and conformational properties) and its biochemical processes (DNA polymerization and the repair of DNA adducts) is remarkable. Hence, we conclude that monodentate DNA binding of PtII compounds may considerably affect the biophysical properties of DNA and consequently downstream cellular processes as a result of a large increase in the bulkiness of the nonleaving ligands in this class of metal complex.

Citovat

NOVÁKOVÁ, Olga, Jaroslav MALINA, Jana KAŠPÁRKOVÁ, Anna HALÁMIKOVÁ, Vladan BERNARD, Francesco INTINI, Giovanni NATILE and Viktor BRABEC. Energetics, conformation and recognition of DNA duplexes modified by methylated analougues of [PtCl(dien)]+. Chemistry – A European Journal. Germany: Wiley, 2009, vol. 2009, No 15, p. 6211-6221. ISSN 0947-6539.

@article{842978,
   author = {Nováková, Olga and Malina, Jaroslav and Kašpárková, Jana and Halámiková, Anna and Bernard, Vladan and Intini, Francesco and Natile, Giovanni and Brabec, Viktor},
   article_location = {Germany},
   article_number = {15},
   keywords = {DNA, DNA recognition, DNA structures, platinum, polymerization},
   language = {eng},
   issn = {0947-6539},
   journal = {Chemistry – A European Journal},
   title = {Energetics, conformation and recognition of DNA duplexes modified by methylated analougues of [PtCl(dien)]+},
   volume = {2009},
   year = {2009}
}

TY  - JOUR
ID  - 842978
AU  - Nováková, Olga - Malina, Jaroslav - Kašpárková, Jana - Halámiková, Anna - Bernard, Vladan - Intini, Francesco - Natile, Giovanni - Brabec, Viktor
PY  - 2009
TI  - Energetics, conformation and recognition of DNA duplexes modified by methylated analougues of [PtCl(dien)]+
JF  - Chemistry – A European Journal
VL  - 2009
IS  - 15
SP  - 6211-6221
EP  - 6211-6221
PB  - Wiley
SN  - 09476539
KW  - DNA, DNA recognition, DNA structures, platinum, polymerization
N2  - In early studies of empirical structure–activity relationships, monodentate PtII complexes were considered to be biologically inactive. Examples of such inactive monodentate PtII compounds are [PtCl (dien)]+ dien=diethylenetriamine) and [PtCl(NH3)3]+. DNA is considered the major biological target of platinum compounds. Thus, monodentate DNA binding of PtII compounds was previously expected to display insignificant biological effects because it was assumed to affect DNA conformation and downstream cellular processes markedly less than the cross-links of bifunctional PtII complexes. More recently it was shown that some monodentate PtII complexes do exhibit biological effects; the active monodentate PtII complexes commonly feature bulkier amine ligands than the hitherto used dien or NH3 groups. We were therefore interested in determining whether a simple but marked enhancement of the bulkiness of the dien ligand in monodentate [Pt (NO3)- (dien)]+ by multiple methylation of this ligand affects the early phases in which platinum compounds exert their biological activity. More specifically, the goals of this study, performed in cell-free media, were to determine how the modification of DNA duplexes by methylated analogues of [Pt (NO3)- (dien)]+ affects their energetics and how the alterations of this biophysical parameter are reflected by the recognition of these duplexes by DNA polymerases and the DNA repair system. We have found that the impact of the methylation of [Pt (NO3) (dien)]+ on the biophysical properties of DNA (thermodynamic, thermal, and conformational properties) and its biochemical processes (DNA polymerization and the repair of DNA adducts) is remarkable. Hence, we conclude that monodentate DNA binding of PtII compounds may considerably affect the biophysical properties of DNA and consequently downstream cellular processes as a result of a large increase in the bulkiness of the nonleaving ligands in this class of metal complex.
ER  -

NOVÁKOVÁ, Olga, Jaroslav MALINA, Jana KAŠPÁRKOVÁ, Anna HALÁMIKOVÁ, Vladan BERNARD, Francesco INTINI, Giovanni NATILE and Viktor BRABEC. Energetics, conformation and recognition of DNA duplexes modified by methylated analougues of [PtCl(dien)]+. \textit{Chemistry – A European Journal}. Germany: Wiley, 2009, vol.~2009, No~15, p.~6211-6221. ISSN~0947-6539.

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