Biophysical analysis of natural, double-helical DNA modified by
a dinuclear platinum(II) organometallic compound in a cell-free
medium

J 2002

Biophysical analysis of natural, double-helical DNA modified by a dinuclear platinum(II) organometallic compound in a cell-free medium

MARINI, Victoria, Jana KAŠPÁRKOVÁ, Olga NOVAKOVA, Luigi MONSU SCOLARO, Raffaello ROMEO et. al.

Basic information

Original name

Biophysical analysis of natural, double-helical DNA modified by a dinuclear platinum(II) organometallic compound in a cell-free medium

Name in Czech

Biofyzikální analýza dvouřetězcová DNA modifikována dinukleární platinovou organometalovou sloučeninou

Authors

MARINI, Victoria (858 Uruguay), Jana KAŠPÁRKOVÁ (203 Czech Republic), Olga NOVAKOVA (203 Czech Republic), Luigi MONSU SCOLARO (380 Italy), Raffaello ROMEO (380 Italy) and Viktor BRABEC (203 Czech Republic, guarantor)

Edition

Journal of Biological Inorganic Chemistry, 2002, 0949-8257

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

References:

URL

Impact factor

Impact factor: 3.911

RIV identification code

RIV/00216224:14310/02:00028886

Organization unit

Faculty of Science

Keywords in English

DNA;Organoplatinum(II);Adducts;Cross-link;Conformation

Abstract

ORIG CZ

V originále

Modifications of natural DNA by the dinuclear platinum(II) organometallic complex [{Pt(Me)Cl(Me2SO)}2(-N-N)] [where N-N=H2N(CH2)6NH2] (ORGANObisPt) were studied by methods of molecular biophysics. These methods include DNA binding studies using atomic absorption spectrophotometry, HPLC analysis of enzymatically digested DNA, interstrand cross-linking employing gel electrophoresis under denaturing conditions, DNA unwinding studied by gel electrophoresis, mapping of DNA adducts by transcription assay, DNA melting curves measured by absorption spectrophotometry and conformational analysis of platinated DNA by differential pulse polarography. The results indicate that the complex ORGANObisPt binds irreversibly to DNA. Its DNA binding mode is, however, different from that of the formally equivalent [{cis-PtCl(NH3)2}2(-N-N)] (1,1/c,c), which exhibits antitumor activity including that in the tumor cells resistant to cisplatin. Interestingly, ORGANObisPt binds to DNA considerably faster than 1,1/c,c and cisplatin. In addition, when ORGANObisPt binds to DNA it exhibits a strong base sequence specificity to guanine residues. ORGANObisPt forms mainly monofunctional adducts on double-helical DNA. It forms also a small amount of DNA interstrand cross-links (~2%), i.e. a radically smaller amount in comparison with the complex 1,1/c,c. Importantly, these interstrand cross-links of ORGANObisPt are capable of terminating RNA synthesis in vitro, while its major monofunctional adducts are not. In addition, the adducts of ORGANObisPt affect the conformation of DNA, but in a different way than its dinuclear analogue 1,1/c,c or cisplatin. Some structural features of ORGANObisPt, such as the charge or nature of the trans and cis activating groups relative to the labile chloride, might be responsible for the altered DNA binding mode and biological activity in comparison with the 1,1/c,c compound.

In Czech

Modifikace DNA dinukleárním platinovým (II) organometalickým komplexem [{Pt(Me)Cl(Me2SO)}2(-N-N)] [kde N-N=H2N(CH2)6NH2] (ORGANObisPt) byly studovány metody molekulární biofyziky.

Links

GA301/00/0556, research and development project

Name: Dvojjaderné komplexy kovů jako agens schopná vytvářet můstky mezi DNA a bílkovinami

GA305/02/1552, research and development project

Name: Oligonukleotidy modifikované komplexy platiny pro selektivní modulaci genové exprese; vztah k "protismyslné" strategii při vývoji nových farmak.

Citovat

MARINI, Victoria, Jana KAŠPÁRKOVÁ, Olga NOVAKOVA, Luigi MONSU SCOLARO, Raffaello ROMEO and Viktor BRABEC. Biophysical analysis of natural, double-helical DNA modified by a dinuclear platinum(II) organometallic compound in a cell-free medium. Journal of Biological Inorganic Chemistry. 2002, vol. 7, No 7, p. 725-734. ISSN 0949-8257.

@article{406361,
   author = {Marini, Victoria and Kašpárková, Jana and Novakova, Olga and Monsu Scolaro, Luigi and Romeo, Raffaello and Brabec, Viktor},
   article_number = {7},
   keywords = {DNA;Organoplatinum(II);Adducts;Cross-link;Conformation},
   language = {eng},
   issn = {0949-8257},
   journal = {Journal of Biological Inorganic Chemistry},
   title = {Biophysical analysis of natural, double-helical DNA modified by a dinuclear platinum(II) organometallic compound in a cell-free medium},
   url = {http://link.springer.de/link/service/journals/00775/contents/02/00347/paper/s00775-002-0347-1ch000.html},
   volume = {7},
   year = {2002}
}

TY  - JOUR
ID  - 406361
AU  - Marini, Victoria - Kašpárková, Jana - Novakova, Olga - Monsu Scolaro, Luigi - Romeo, Raffaello - Brabec, Viktor
PY  - 2002
TI  - Biophysical analysis of natural, double-helical DNA modified by a dinuclear platinum(II) organometallic compound in a cell-free medium
JF  - Journal of Biological Inorganic Chemistry
VL  - 7
IS  - 7
SP  - 725
EP  - 725
SN  - 09498257
KW  - DNA;Organoplatinum(II);Adducts;Cross-link;Conformation
UR  - http://link.springer.de/link/service/journals/00775/contents/02/00347/paper/s00775-002-0347-1ch000.html
N2  - Modifications of natural DNA by the dinuclear platinum(II) organometallic complex [{Pt(Me)Cl(Me2SO)}2(-N-N)] [where N-N=H2N(CH2)6NH2] (ORGANObisPt) were studied by methods of molecular biophysics. These methods include DNA binding studies using atomic absorption spectrophotometry, HPLC analysis of enzymatically digested DNA, interstrand cross-linking employing gel electrophoresis under denaturing conditions, DNA unwinding studied by gel electrophoresis, mapping of DNA adducts by transcription assay, DNA melting curves measured by absorption spectrophotometry and conformational analysis of platinated DNA by differential pulse polarography. The results indicate that the complex ORGANObisPt binds irreversibly to DNA. Its DNA binding mode is, however, different from that of the formally equivalent [{cis-PtCl(NH3)2}2(-N-N)] (1,1/c,c), which exhibits antitumor activity including that in the tumor cells resistant to cisplatin. Interestingly, ORGANObisPt binds to DNA considerably faster than 1,1/c,c and cisplatin. In addition, when ORGANObisPt binds to DNA it exhibits a strong base sequence specificity to guanine residues. ORGANObisPt forms mainly monofunctional adducts on double-helical DNA. It forms also a small amount of DNA interstrand cross-links (~2%), i.e. a radically smaller amount in comparison with the complex 1,1/c,c. Importantly, these interstrand cross-links of ORGANObisPt are capable of terminating RNA synthesis in vitro, while its major monofunctional adducts are not. In addition, the adducts of ORGANObisPt affect the conformation of DNA, but in a different way than its dinuclear analogue 1,1/c,c or cisplatin. Some structural features of ORGANObisPt, such as the charge or nature of the trans and cis activating groups relative to the labile chloride, might be responsible for the altered DNA binding mode and biological activity in comparison with the 1,1/c,c compound.
ER  -

MARINI, Victoria, Jana KAŠPÁRKOVÁ, Olga NOVAKOVA, Luigi MONSU SCOLARO, Raffaello ROMEO and Viktor BRABEC. Biophysical analysis of natural, double-helical DNA modified by a dinuclear platinum(II) organometallic compound in a cell-free medium. \textit{Journal of Biological Inorganic Chemistry}. 2002, vol.~7, No~7, p.~725-734. ISSN~0949-8257.

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