Cargando…

Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC)·d(GAGAGCGAGG)

The single-stranded oligonucleotide 5′-d(CCTCGCTCTC) (I) was reacted with the antitumor trans platinum iminoderivative trans-[PtCl(2){E-HN = C(OMe)Me}(2)] (trans-EE) and subsequently annealed with its complementary strand 5′-d(GAGAGCGAGG) (II). The platinated duplex was characterized by 1D and 2D pr...

Descripción completa

Detalles Bibliográficos
Autores principales: Andersen, Bjørn, Margiotta, Nicola, Coluccia, Mauro, Natile, Giovanni, Sletten, Einar
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365194/
https://www.ncbi.nlm.nih.gov/pubmed/18475920
http://dx.doi.org/10.1155/MBD.2000.23
_version_ 1782154109371023360
author Andersen, Bjørn
Margiotta, Nicola
Coluccia, Mauro
Natile, Giovanni
Sletten, Einar
author_facet Andersen, Bjørn
Margiotta, Nicola
Coluccia, Mauro
Natile, Giovanni
Sletten, Einar
author_sort Andersen, Bjørn
collection PubMed
description The single-stranded oligonucleotide 5′-d(CCTCGCTCTC) (I) was reacted with the antitumor trans platinum iminoderivative trans-[PtCl(2){E-HN = C(OMe)Me}(2)] (trans-EE) and subsequently annealed with its complementary strand 5′-d(GAGAGCGAGG) (II). The platinated duplex was characterized by 1D and 2D proton NMR spectroscopy at 600 MHz. In agreement with previous studies by different techniques trans-EE was found to form a monofunctional adduct with the duplex involving the guanine residue. The modification by trans-EE has been found to induce only minor local distortion in the duplex geometry. Two key crosspeaks observed in the NOESY map corresponding to a close contact between G5-H8 and the methoxy and the methyl group, respectively, enabled us to dock the trans-EE complex with the duplex by geometry optimization. The results support the idea that the antitumor activity of trans-EE is related to lesion of DNA fundamentally different from that of cisplatin. Unexpectedly, the NOESY spectra indicated that at the high NaCl concentration used (0.2 M) the duplex was found to undergo slow deplatination. This was subsequently proved by HPLC. In a separate experiment on platination of the single strand in a salt free environment the HPLC analysis showed that the monofunctional adduct was not deplatinated, however, after 24 hours, additidnal minor isomers were detected.
format Text
id pubmed-2365194
institution National Center for Biotechnology Information
language English
publishDate 2000
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-23651942008-05-12 Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC)·d(GAGAGCGAGG) Andersen, Bjørn Margiotta, Nicola Coluccia, Mauro Natile, Giovanni Sletten, Einar Met Based Drugs Research Article The single-stranded oligonucleotide 5′-d(CCTCGCTCTC) (I) was reacted with the antitumor trans platinum iminoderivative trans-[PtCl(2){E-HN = C(OMe)Me}(2)] (trans-EE) and subsequently annealed with its complementary strand 5′-d(GAGAGCGAGG) (II). The platinated duplex was characterized by 1D and 2D proton NMR spectroscopy at 600 MHz. In agreement with previous studies by different techniques trans-EE was found to form a monofunctional adduct with the duplex involving the guanine residue. The modification by trans-EE has been found to induce only minor local distortion in the duplex geometry. Two key crosspeaks observed in the NOESY map corresponding to a close contact between G5-H8 and the methoxy and the methyl group, respectively, enabled us to dock the trans-EE complex with the duplex by geometry optimization. The results support the idea that the antitumor activity of trans-EE is related to lesion of DNA fundamentally different from that of cisplatin. Unexpectedly, the NOESY spectra indicated that at the high NaCl concentration used (0.2 M) the duplex was found to undergo slow deplatination. This was subsequently proved by HPLC. In a separate experiment on platination of the single strand in a salt free environment the HPLC analysis showed that the monofunctional adduct was not deplatinated, however, after 24 hours, additidnal minor isomers were detected. Hindawi Publishing Corporation 2000 /pmc/articles/PMC2365194/ /pubmed/18475920 http://dx.doi.org/10.1155/MBD.2000.23 Text en Copyright © 2000 Hindawi Publishing Corporation. http://creativecommons.org/licenses/by/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Andersen, Bjørn
Margiotta, Nicola
Coluccia, Mauro
Natile, Giovanni
Sletten, Einar
Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC)·d(GAGAGCGAGG)
title Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC)·d(GAGAGCGAGG)
title_full Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC)·d(GAGAGCGAGG)
title_fullStr Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC)·d(GAGAGCGAGG)
title_full_unstemmed Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC)·d(GAGAGCGAGG)
title_short Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC)·d(GAGAGCGAGG)
title_sort antitumor trans platinum dna adducts: nmr and hplc study of the interaction between a trans-pt iminoether complex and the deoxy decamer d(cctcgctctc)·d(gagagcgagg)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365194/
https://www.ncbi.nlm.nih.gov/pubmed/18475920
http://dx.doi.org/10.1155/MBD.2000.23
work_keys_str_mv AT andersenbjørn antitumortransplatinumdnaadductsnmrandhplcstudyoftheinteractionbetweenatransptiminoethercomplexandthedeoxydecamerdcctcgctctcdgagagcgagg
AT margiottanicola antitumortransplatinumdnaadductsnmrandhplcstudyoftheinteractionbetweenatransptiminoethercomplexandthedeoxydecamerdcctcgctctcdgagagcgagg
AT colucciamauro antitumortransplatinumdnaadductsnmrandhplcstudyoftheinteractionbetweenatransptiminoethercomplexandthedeoxydecamerdcctcgctctcdgagagcgagg
AT natilegiovanni antitumortransplatinumdnaadductsnmrandhplcstudyoftheinteractionbetweenatransptiminoethercomplexandthedeoxydecamerdcctcgctctcdgagagcgagg
AT sletteneinar antitumortransplatinumdnaadductsnmrandhplcstudyoftheinteractionbetweenatransptiminoethercomplexandthedeoxydecamerdcctcgctctcdgagagcgagg