Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied
by NMR Spectroscopy and Molecular Dynamics Simulations

J 2009

Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied by NMR Spectroscopy and Molecular Dynamics Simulations

TELETCHEA, Stephane; Tormod SKAUGE; Einar SLETTEN a Jiří KOZELKA

Základní údaje

Originální název

Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied by NMR Spectroscopy and Molecular Dynamics Simulations

Autoři

TELETCHEA, Stephane; Tormod SKAUGE; Einar SLETTEN a Jiří KOZELKA

Vydání

Chemistry - A European Journal, Weinheim, WILEY-VCH Verlag GmbH & Co. KGaA, 2009, 0947-6539

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10400 1.4 Chemical sciences

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.382

Označené pro přenos do RIV

Ano

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

antitumor agents; DNA structures; molecular modeling; NMR spectroscopy; platinum

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 17. 6. 2020 14:46, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

The antitumor drug cisplatin (cis-[PtCl(2)(NH(3))(2)]) reacts with cellular DNA to form GG intrastrand adducts between adjacent guanines as predominant lesions. GGG sites have been shown to be hotspots of platination. To study the structural perturbation induced by binding of cisplatin to two adjacent guanines of a GGG trinucleotide, we examined here the decanucleotide duplex d[(G(1)C(2)C(3)G(4)*G(5)*G(6)T(7)-C(8)G(9)C(10))center dot d(G(11)C(12)G(13)A(14)C(15)C(16)C(17)G(18)G(19)C(20))] (dsCG*G*G) intrastrand cross-linked at the G* guanines by cis-{Pt(NH(3))(2)}(2+) using NMR spectroscopy and molecular dynamics (MD) simulations. The NMR spectra of dsCG*G*G were found to be similar to those of previously characterized DNA duplexes cross-linked by cisplatin at a pyG*G*X site (py=pyrimidine; X=C, T, A). This similarity of NMR spectra indicates that the base at the 3'-side of the G*G*-Pt cross-link does not affect the structure to a large extent. An unprecedented reversible isomerization between the duplex dsCG*G*G (bearing a G(4)*G(5)*-Pt chelate and duplex dsGG*G*T (bearing a G(5)*G(6)*-Pt chelate) was observed, which yielded a 40:60 equilibrium between the two intrastrand GG-Pt cross-links. No formation of interstrand cross-links was observed. NMR spectroscopic data of dsCG*G*G indicated that the deoxyribose of the 5'-G* adopts an N-type conformation, and the cytidines C(3), C(15), and C(16) have average phase angles intermediate between S and N. The NMR spectroscopic chemical shifts of dsGG*G*T showed some fundamental differences to those of pyG*G*-platinum adducts but were in agreement with the NMR spectra reported previously for the DNA duplexes crosslinked at an AG*G*C sequence by cisplatin or oxaliplatin. The presence of a purine instead of a pyrimidine at the 5'-side of the G*G* cross-link seems therefore to affect the structure of the XG* step significantly.

Citovat

TELETCHEA, Stephane; Tormod SKAUGE; Einar SLETTEN a Jiří KOZELKA. Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied by NMR Spectroscopy and Molecular Dynamics Simulations. Chemistry - A European Journal. Weinheim: WILEY-VCH Verlag GmbH & Co. KGaA, 2009, roč. 15, č. 45, s. 12320-12337. ISSN 0947-6539. Dostupné z: https://doi.org/10.1002/chem.200901158.

@article{1662897,
   author = {Teletchea, Stephane and Skauge, Tormod and Sletten, Einar and Kozelka, Jiří},
   article_location = {Weinheim},
   article_number = {45},
   doi = {https://doi.org/10.1002/chem.200901158},
   keywords = {antitumor agents; DNA structures; molecular modeling; NMR spectroscopy; platinum},
   language = {eng},
   issn = {0947-6539},
   journal = {Chemistry - A European Journal},
   title = {Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied by NMR Spectroscopy and Molecular Dynamics Simulations},
   url = {https://doi.org/10.1002/chem.200901158},
   volume = {15},
   year = {2009}
}

TY  - JOUR
ID  - 1662897
AU  - Teletchea, Stephane - Skauge, Tormod - Sletten, Einar - Kozelka, Jiří
PY  - 2009
TI  - Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied by NMR Spectroscopy and Molecular Dynamics Simulations
JF  - Chemistry - A European Journal
VL  - 15
IS  - 45
SP  - 12320-12337
EP  - 12320-12337
PB  - WILEY-VCH Verlag GmbH & Co. KGaA
SN  - 09476539
KW  - antitumor agents
KW  - DNA structures
KW  - molecular modeling
KW  - NMR spectroscopy
KW  - platinum
UR  - https://doi.org/10.1002/chem.200901158
L2  - https://doi.org/10.1002/chem.200901158
N2  - The antitumor drug cisplatin (cis-[PtCl(2)(NH(3))(2)]) reacts with cellular DNA to form GG intrastrand adducts between adjacent guanines as predominant lesions. GGG sites have been shown to be hotspots of platination. To study the structural perturbation induced by binding of cisplatin to two adjacent guanines of a GGG trinucleotide, we examined here the decanucleotide duplex d[(G(1)C(2)C(3)G(4)*G(5)*G(6)T(7)-C(8)G(9)C(10))center dot d(G(11)C(12)G(13)A(14)C(15)C(16)C(17)G(18)G(19)C(20))] (dsCG*G*G) intrastrand cross-linked at the G* guanines by cis-{Pt(NH(3))(2)}(2+) using NMR spectroscopy and molecular dynamics (MD) simulations. The NMR spectra of dsCG*G*G were found to be similar to those of previously characterized DNA duplexes cross-linked by cisplatin at a pyG*G*X site (py=pyrimidine; X=C, T, A). This similarity of NMR spectra indicates that the base at the 3'-side of the G*G*-Pt cross-link does not affect the structure to a large extent. An unprecedented reversible isomerization between the duplex dsCG*G*G (bearing a G(4)*G(5)*-Pt chelate and duplex dsGG*G*T (bearing a G(5)*G(6)*-Pt chelate) was observed, which yielded a 40:60 equilibrium between the two intrastrand GG-Pt cross-links. No formation of interstrand cross-links was observed. NMR spectroscopic data of dsCG*G*G indicated that the deoxyribose of the 5'-G* adopts an N-type conformation, and the cytidines C(3), C(15), and C(16) have average phase angles intermediate between S and N. The NMR spectroscopic chemical shifts of dsGG*G*T showed some fundamental differences to those of pyG*G*-platinum adducts but were in agreement with the NMR spectra reported previously for the DNA duplexes crosslinked at an AG*G*C sequence by cisplatin or oxaliplatin. The presence of a purine instead of a pyrimidine at the 5'-side of the G*G* cross-link seems therefore to affect the structure of the XG* step significantly.
ER  -

TELETCHEA, Stephane; Tormod SKAUGE; Einar SLETTEN a Jiří KOZELKA. Cisplatin Adducts on a GGG Sequence within a DNA Duplex Studied by NMR Spectroscopy and Molecular Dynamics Simulations. \textit{Chemistry - A European Journal}. Weinheim: WILEY-VCH Verlag GmbH \&{} Co. KGaA, 2009, roč.~15, č.~45, s.~12320-12337. ISSN~0947-6539. Dostupné z: https://doi.org/10.1002/chem.200901158.

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