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A radical way to link DNA strands The nucleotide radical shown, generated selectively in a synthetic DNA, efficiently cross-links to its complement nucleotide, a new study shows (J. Am. Chem. Soc., 2005, 127, 3692). A number of anticancer drugs, including mitomycin C, owe their cytotoxity to the ability to form DNA interstrand cross-links. The finding, by In Seok Hong and Marc M. Greenberg of Johns Hopkins University, presents a new path for designing anticancer agents. Because this nucleotide radical is formed during irradiation of DNA, the finding also helps to explain how cancer cells are killed by radiation therapy. That the cross-link is formed with the complement nucleotide is unusual and potentially also of therapeutic importance. Cells probably repair cross-links, but when the cross-link is between complement nucleotides, the repair might lead to loss of information and could result in even more damage, Greenberg thinks. "This is something we need to investigate," he says. For now, "we have shown a very efficient pathway for forming cross-links," he adds. "You can now imagine how an organic chemist might ask, 'How can I generate this radical in a manner that could be more compatible with cellular conditions?' " |
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