ORGN 421 |
| Interstrand DNA cross-links exert significant biological effects. For instance, DNA interstrand cross-links (ISC) are believed to be the main source of the cytotoxicity of many antitumor agents such as mitomycin C and nitrogen mustards. In each instance, DNA ISC formation is mediated by a molecule, which forms a covalent bond to each strand. We found efficient DNA ISC formation by the radical resulting from formal hydrogen atom abstraction from the thymine methyl group, 5-(2'-deoxyuridinyl)methyl radical (1). Photolysis of duplex DNA containing phenylselenide 2, or aryl sulfides 3 and 4 produced interstrand DNA cross-links irrespective of the presence of oxygen. This is the first example in which formation of a DNA radical produced an interstrand cross-link directly. We also found that γ-radiolysis of the DNA duplex containing phenylselenide 2 produced DNA ISC under hypoxic conditions. This is also the first example in which γ-radiolysis of DNA containing a radical precursor resulted in interstrand cross-links. The respective deoxynucleotide triphosphate of the phenylselenide 2 is efficiently incorporated by klenow exo-, suggesting this molecule may be useful as a radiosensitizing agent.
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Bioorganic, Metal-Mediated Reactions, and Molecular Recognition
8:00 PM-10:00 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- Hall A, Poster
Division of Organic Chemistry |
