An NMR study and crystal structure of [{cis-Pt(NH3)2(9EtG-κN7)}2(μ-pz)][NO3]3 (9EtG = 9-ethylguanine) as a model compound for the 1,2-intrastrand GG crosslink †

Komeda, Seiji; Ohishi, Hirofumi; Yamane, Hirotoshi; Harikawa, Michinori; Sakaguchi, K.; Chikuma, Masahiko

doi:10.1039/a903081f

Cited by 60 publications

(68 citation statements)

References 14 publications

(8 reference statements)

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“…The unplatinated ssI (charge À9) elutes at 11.00 min, and the newly formed platinated single strand (ssIII) containing the Pt-pz-Pt 1,2-intrastrand cross-link elutes at 9.02 min, in agreement with its reduced negative charge of À6. As in the case of the reactions with 9-ethylguanine [25] and 5'-GMP, [26] no intermediate species are observed. After three days the peak corresponding to ssI had almost completely disappeared and ssIII had formed in 90 % yield.…”

Section: Resultsmentioning

confidence: 60%

“…FPLC chromatography was performed on a BioLogic HR chromatography system (BioRad). 2 was synthesized as described previously [25] 2 and pyrazole. The complex was allowed to react with the purine-rich oligonucleotide (ssI) (6 mg) in a 1:1 ratio in H 2 O (1 mL).…”

Section: Methodsmentioning

confidence: 99%

“…[25] In this structure, the two 9-ethylguanines are stacked in a way which suggests that incorporation of such a cross-link into B-DNA would cause relatively minor distortions, in contrast to the 1,2-GG intrastrand cross-links formed by cisplatin. Thus, 1 is the first cytotoxic complex whose design rationale was based on envisioning a specific structural distortion caused upon binding to DNA, that is, avoiding a significant curvature of the DNA helix.…”

Section: A C H T U N G T R E N N U N G (M-pz)]mentioning

confidence: 97%

“…Following this idea, Kozelka et al [22] have synthesized dinuclear hydrazine-bridged complexes that are highly cytotoxic in vitro but have no activity in animal models. More promising compounds based on this strategy are the azolato-bridged dinuclear platinum complexes recently reported by Komeda et al [23][24][25] In particular, the complex [(cis-{Pt-A C H T U N G T R E N N U N G (NH 3 ) 2 }) 2 …”

Section: A C H T U N G T R E N N U N G (M-oh)a C H T U N G T R E N N mentioning

confidence: 99%

“…The bond lengths and bond angles were taken from the crystal structure of [(cis-{PtA C H T U N G T R E N N U N G (NH 3 ) 2 }(9-ethylguanine)) 2 A C H T U N G T R E N N U N G (m-pz)] 3 + , [25] and the corresponding force constants were equivalenced to those of the five-membered ring of histidine. The same parameters were used for the PtÀN-A C H T U N G T R E N N U N G (pyrazole) bonds as for the PtÀNA C H T U N G T R E N N U N G (guanine) bonds.…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

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A Pyrazolato‐Bridged Dinuclear Platinum(II) Complex Induces Only Minor Distortions upon DNA‐Binding

Téletchéa

Komeda

Teuben

et al. 2006

Chemistry A European J

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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 complex that has been successfully designed by envisioning the structural consequences of its binding to DNA.

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Section: Resultsmentioning

confidence: 60%

Section: Methodsmentioning

confidence: 99%

Section: A C H T U N G T R E N N U N G (M-pz)]mentioning

confidence: 97%

Section: A C H T U N G T R E N N U N G (M-oh)a C H T U N G T R E N N mentioning

confidence: 99%

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

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A Pyrazolato‐Bridged Dinuclear Platinum(II) Complex Induces Only Minor Distortions upon DNA‐Binding

Téletchéa

Komeda

Teuben

et al. 2006

Chemistry A European J

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Platinum‐Based Anticancer DrugsBased in part on the article Platinum‐Based Anticancer Drugs by Steven J. Brown, Christine S. Chow & Stephen J. Lippard which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.

Robillard

Reedijk

2005

Encyclopedia of Inorganic Chemistry

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The chemotherapeutic agent cisplatin enjoys the status of one of the world's best‐selling anticancer drugs. As is the case with other chemotherapeutic drugs, however, cisplatin has its drawbacks, including intrinsic or acquired resistance and toxicity. Efforts to mitigate cisplatin's drawbacks have inspired the synthesis of myriad analogs, but with only a handful that have been shown to be acceptable for clinical application. Increased understanding of the mechanism of the action of cisplatin, as a result of decades of research, is leading to a more rational design of new platinum drugs. However, the incomplete puzzle of cisplatin's ways and the lack of a single decisive biological target for anticancer treatment still complicate the search for improved platinum drugs. This article gives a brief introduction to cisplatin, and subsequently summarizes and evaluates the development of cisplatin derivatives and possible new approaches.

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Role of Metallodrugs in Medicinal Inorganic Chemistry

Kumar

Kant

et al. 2020

Advances in Metallodrugs

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An NMR study and crystal structure of [{cis-Pt(NH3)2(9EtG-κN7)}2(μ-pz)][NO3]3 (9EtG = 9-ethylguanine) as a model compound for the 1,2-intrastrand GG crosslink †

Cited by 60 publications

References 14 publications

A Pyrazolato‐Bridged Dinuclear Platinum(II) Complex Induces Only Minor Distortions upon DNA‐Binding

A Pyrazolato‐Bridged Dinuclear Platinum(II) Complex Induces Only Minor Distortions upon DNA‐Binding

Platinum‐Based Anticancer DrugsBased in part on the article Platinum‐Based Anticancer Drugs by Steven J. Brown, Christine S. Chow & Stephen J. Lippard which appeared in theEncyclopedia of Inorganic Chemistry, First Edition.

Role of Metallodrugs in Medicinal Inorganic Chemistry

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