UVA‐Photosensitivityof cis‐Diamminedichloro‐Platinum(II)‐Modified DNA

Payet, Dominique; Leng, Marc

doi:10.1155/mbd.1995.137

Cited by 8 publications

(3 citation statements)

References 2 publications

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“…Irradiation of DNA modified by cisplatin with UV light (l b 300 nm) can induce specific cross-links to the protein HMG1, thought to involve Lys6 in domain B with labilization of a Pt ± purine bond. [137,138] …”

Section: Photoactivationmentioning

confidence: 99%

Metals in Medicine

Guo

Sadler

1999

Angew. Chem. Int. Ed.

839

504

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Not only the 24 or so essential elements, but also nonessential and even radioactive elements have enormous potential for applications in medicine. In the fight against cancer cisplatin, one of the world's best selling anticancer drugs, is being joined by other platinum, titanium, and ruthenium complexes. Gadolinium(III) complexes can be safely injected as magnetic resonance imaging contrast agents, and ligand design allows targeting of paramagnetic ions as well as radiodiagnostic (e.g. Tc) and radiotherapeutic isotopes (e.g. Re). Manganese superoxide dismutase mimics, vanadium insulin mimics, ruthenium nitric oxide scavengers, lanthanide-based photosensitizers, and metal-targeted organic agents show exciting clinical potential.

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Section: Photoactivationmentioning

confidence: 99%

Metals in Medicine

Guo

Sadler

1999

Angew. Chem. Int. Ed.

839

504

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“…The mechanism of the photoreaction of platinum(II) bound to DNA in a protein complex has been discussed previously (32). Upon irradiation, a platinum-guanine bond dissociates to give a reactive intermediate (39), which then coordinates to a wellpositioned amino acid residue in the HMG-domain protein. DNA-DNA interstrand cross-links also form when the irradiation is performed with 302 nm light, possibly because the base in the opposite strand is similarly activated by the broad dispersion of the irradiation wavelength of the transilluminator bulb as a light source.…”

Section: Discussionmentioning

confidence: 99%

Laser-Induced Photo-Cross-Linking of Cisplatin-Modified DNA to HMG-Domain Proteins

Mikata

Lippard

2001

Biochemistry

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Laser-induced photo-cross-linking was investigated for DNA, modified with cisplatin at specific sites, bound to structure-specific recognition domains of proteins in the high-mobility group (HMG) class. The efficiency of photo-cross-linking depends on the wavelength and power of the laser, the nature of the protein domain, and the oligodeoxyribonucleotide sequences flanking the platinated site. Introduction of 5-iodouridine at thymine sites of the oligodeoxyribonucleotide as an additional photoreactive group did not increase the photo-cross-linking yield. Formation of platinum-mediated DNA-DNA interstrand cross-linking observed previously upon irradiation with 302 nm light [Kane, S. A., and Lippard, S. J. (1996) Biochemistry 35, 2180-2188] was significantly reduced with laser irradiation. HMG1 domain B is superior to domain A for platinum-mediated photo-cross-linking, a result attributed to the different positioning of the proteins with respect to the platinum adduct and the greater ability of domain B to access photolabilized platinum in the major groove. Studies with proteins containing specifically mutated amino acids, and with DNA probes in which the sequences flanking the platinum cross-link site were varied, suggest that the most effective photo-cross-linking occurs for protein domains bound symmetrically and flexibly to cisplatin-modified DNA. The thermodynamic equilibrium between the protein-platinated DNA complex and its components, revealed in gel electrophoretic mobility shift assays (EMSAs), is significantly shifted to the right upon irreversible photo-cross-linking. Thus, only upon photo-cross-linking can the interaction of cisplatin-DNA 1,3-intrastrand d(GpTpG) or interstrand cross-links with HMG1 domain B protein be detected. Photo-cross-linking is thus an effective tool for investigating the interaction of cisplatin-modified DNA with damage-recognition proteins under heterogeneous conditions such those in cell extracts or living cells.

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“…Bestrahlt man eine mit Cisplatin modifizierte DNA mit UV-Licht (l b 300 nm), lassen sich spezifische Vernetzungen zum Protein HMG1 induzieren, wobei man annimmt, daû Lys6 in der B-Domäne beteiligt ist und die Pt-Purin-Bindung labilisiert wird. [137,138] …”

Section: Photoaktivierungunclassified

Metalle in der Medizin

1999

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Nicht nur die etwa 24 essentiellen Elemente, sondern auch nichtessentielle und sogar radioaktive Elemente verfügen über ein enormes medizinisches Potential. Im Kampf gegen Krebs steht Cisplatin, eines der meistverkauften Cytostatica, nicht allein: Andere Platin‐ sowie Ruthenium‐ und Titankomplexe werden ebenfalls eingesetzt. Gadolinium(III)‐Komplexe können gefahrlos als Kontrastmittel für die NMR‐Mikroskopie genutzt werden, und mit den „richtigen”︁ Liganden ist die gezielte Freisetzung von paramagnetischen Ionen sowie von radiodiagnostischen (z. B. 99mTc) und radiotherapeutischen Isotopen (z. B. 186Re) möglich. Superoxid‐Dismutase‐Mimetica auf Manganbasis, Insulin‐Mimetica auf Vanadiumbasis, NO‐Fänger auf Rutheniumbasis, Photosensibilisatoren auf Lanthanoidbasis und organische Verbindungen, die gezielt mit Metallionen reagieren, zeigen ein faszinierendes medizinisches Potential.

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UVA‐Photosensitivityof cis‐Diamminedichloro‐Platinum(II)‐Modified DNA

Cited by 8 publications

References 2 publications

Metals in Medicine

Metals in Medicine

Laser-Induced Photo-Cross-Linking of Cisplatin-Modified DNA to HMG-Domain Proteins

Metalle in der Medizin

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