COVALENT STRUCTURE OF THE DNA-DNA INTERSTRAND CROSS-LINK FORMED BY REDUCTIVELY ACTIVATED FR66979 IN SYNTHETIC DNA DUPLEXES

The lesion responsible for the dG-to-dG, DNA-DNA interstrand cross-link formed at the duplex dinucleotide sequence 5'-d(CG) by reductively activated FR66979 (2) was isolated from the cross-linked synthetic oligonucleotide duplex [5'-d(TATACGTATA)](2). The lesion and a peracetylated derivative of this substance were studied by mass, UV, and H-1 NMR (2D PS COSY and 1D NOE) spectroscopies. The data overwhelmingly support the proposal that this lesion possesses the mitosene-like structure 8, the analog of the lesion 5a formed in DNA by reductively activated mitomycin C. This finding offers in vitro support for the proposal of in vivo bioreductive activation of these substances as the prelude to DNA-DNA interstrand cross-linking.