DNA cross-link

The key to hexavalent chromium s mutagenicity and possible carcinogenicity is the abiHty of this oxidation state to penetrate the cell membrane. The Cr(VI) Species promotes DNA strand breaks and initiates DNA—DNA and DNA-protein cross-links both in cell cultures and in vivo (105,112,128—130). The mechanism of this genotoxic interaction may be the intercellular reduction of Cr(VI) in close proximity to the nuclear membrane. When in vitro reductions of hexavalent chromium are performed by glutathione, the formation of Cr(V) and glutathione thiyl radicals are observed, and these are beHeved to be responsible for the formation of the DNA cross-links (112). 

DNA cross-linking agents (mainly heterocycles) as antitumor drugs 98CRV2723. 

Natural and synthetic heterocycles as DNA cross-linking agents and antitumor drugs 98CRV2723. 

Oxo-G (81), spiroaminodihydantoin (83), and guanidinohydantoin (85) are mutagenic lesions in duplex DNA. ° Interestingly, the electrophilic intermediate generated upon oxidation 8-oxo-G can yield protein-DNA cross-links. ... 

Richter, S. N. Maggi, S. Colloredo-Mels, S. Palumbo, M. Freccero, M. Binol quinone methides as bisalkylating and DNA cross-linking agents. J. Am. Chem. Soc. 2004, 126, 13973-13979. 

Verga, D. Richter, S. N. Palumbo, M. Gandolfi, R. Freccero, M. Bipyridyl ligands as photoactivatable mono- and bis-alkylating agents capable of DNA cross-linking. Org. Biomol. Chem. 2007, 5, 233-235. 

Ping, W. Yang, S. Lixia, Z. Hanping, H. Xiang, Z. Quinone methide derivatives important intermediates to DNA alkylating and DNA cross-linking actions. Curr. Med. Chem. 2005, 12, 2893-2913. 

Kohn, K. W. Beyond DNA cross-linking history and prospects of DNA-targeted cancer treatment—Fifteenth Bruce F. Cain Memorial Award Lecture. Cancer Res. 1996, 56, 5533-5546. 

The Reversibility of Quinone Methide Reaction Does Not Preclude Its Use in Forming DNA Cross-Links... 

SCHEME 9.16 DNA cross-linking by tandem quinone methide formation. 

The reversibility of DNA cross-linking by the QMPs illustrated in Fig. 9.4 has not been examined directly but is presumably controlled as before by the leaving group strength of the DNA nucleophiles and the electronic characteristics of the QM intermediates. Unless both possible QMs form simultaneously, the cross-linking agents still remain bound to DNA at one site as the other is transiently released during... 

FIGURE 9.4 Representative quinone methide precursors for DNA cross-linking.61 66... 

SCHEME 9.17 DNA cross-linking by a quinone methide-acridine conjugate. 

Kumar, D. Veldhuyzen, W. F. Zhou, Q. Rokita, S. E. Conjugation of a hairpin pyrrole-imidazole polyamide to a quinone methide for control of DNA cross-linking. Bioconjug. Chem. 2004, 15, 915-922. 

Hambley and co-workers have reported the synthesis, DNA cross-linking, and in vitro anticancer properties of a platinum(II) complex that was designed to bind the macromolecule in an interstrand rather than intrastrand manner,162 the latter being the dominant mode of DNA-binding by platinum anticancer drugs such as cisplatin. The complex [PtCl2(hpip)] ((46) ... 

Oxaliplatin - alkylating agent causes DNA cross-linking... 

Owing to their unique (tunable-electronic) properties, semiconductor (quantum dots) nanocrystals have generated considerable interest for optical DNA detection [12], Recent activity has demonstrated the utility of quantum dot nanoparticles for enhanced electrical DNA detection [33, 34, 50], Willner et al. reported on a photoelectrochemical transduction of DNA sensing events in connection with DNA cross-linked CdS nanoparticle arrays [50], The electrostatic binding of the Ru(NH3)63+ electron acceptor to the dsDNA... 

I. Willner, P. Patolsky, and J. Wasserman, Photoelectrochemistry with controlled DNA-cross-linked CdS nanoparticle arrays. Angew. Chem. Int. Ed. 40, 1861-1864 (2001). 

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