A pyrazolato-bridged dinuclear platinum(II) complex induces only minor distortions upon DNA-binding

Chemistry : a European Journal
Stéphane TeletchéaJiří Kozelka

Abstract

The cytotoxic, pyrazolato-bridged dinuclear platinum(II) complex [(cis-{Pt(NH3)2})2(mu-OH)(mu-pz)]2+ (pz=pyrazolate) has been found to cross-link two adjacent guanines of a double-stranded DNA decamer without destabilizing the duplex and without changing the directionality of the helix axis. A 1H NMR study of the oligonucleotide d(CTCTG*G*TCTC)-d(GAGACCAGAG), cross-linked at the two G* guanines by [(cis-{Pt(NH3)2})2(mu-pz)]3+, and molecular dynamics simulations of the explicitly solvated duplex were performed to characterize the structural details of the adduct. The dinuclear platinum cross-link unwinds the helix by approximately 15 degrees , that is, to a similar extent as the widely used antitumor drug cisplatin, but, in contrast to the latter, induces no significant bend in the helix axis. The Watson-Crick base-pairing remains intact, and the melting temperature of the duplex is unaffected by the cross-link. The helical twist is considerably reduced between the two platinated bases, as becomes manifest in an unusually short sequential H1'-H1' distance. This unwinding also affects the sugar ring of the guanosine in the 3'-position to the cross-link, which presents an N<-->S equilibrium. This is the first cytotoxic platinum co...Continue Reading

References

Nov 26, 1990·European Journal of Biochemistry·F HermanJ C Chottard
Feb 1, 1989·Journal of Biomolecular Structure & Dynamics·R Lavery, H Sklenar
Dec 1, 1988·European Journal of Biochemistry·F J Van de Ven, C W Hilbers
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·D R DuckettP Modrich
Apr 27, 1999·Journal of Biomolecular Structure & Dynamics·T E CheathamP A Kollman
Nov 10, 2000·Chemistry : a European Journal·J A ParkinsonP J Sadler
Nov 14, 2001·The Journal of Biological Chemistry·Zoran Z ZdraveskiMartin G Marinus
Dec 20, 2002·Nucleic Acids Research·Péter VárnaiBrigitte Hartmann
Mar 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jan Reedijk
Apr 2, 2004·Nature·A DunhamM T Ross
Jun 1, 1999·Angewandte Chemie·Zijian Guo, Peter J Sadler

❮ Previous
Next ❯

Citations

Dec 22, 2009·Dalton Transactions : an International Journal of Inorganic Chemistry·Katherine S Lovejoy, Stephen J Lippard
Mar 3, 2012·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Seiji Komeda
Nov 12, 2015·International Journal of Molecular Sciences·Gaëlle Savreux-LengletMarie-Hélène David-Cordonnier
Aug 21, 2010·Journal of Nucleic Acids·Gaëlle Lenglet, Marie-Hélène David-Cordonnier
Jan 6, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Alycia M PalmerClaudia Turro
Nov 28, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Tobias RehmRainer Schobert
Aug 21, 2007·Journal of Computational Chemistry·Katrin SpiegelMichael L Klein
May 8, 2010·Dalton Transactions : an International Journal of Inorganic Chemistry·José RuizChristoph Janiak
Jun 23, 2006·Organic & Biomolecular Chemistry·Katrin Spiegel, Alessandra Magistrato
Oct 9, 2009·Chemistry : a European Journal·Stéphane TéletchéaJirí Kozelka
Sep 19, 2012·Chemistry : a European Journal·Jimmy Suryadi, Ulrich Bierbach
Dec 22, 2007·Dalton Transactions : an International Journal of Inorganic Chemistry·Michael A JakupecBernhard K Keppler
Jul 12, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Sara PiccinonnaGiovanni Natile

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.