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(1R,2R-Diaminocyclohexane)oxalatoplatinum(II) (oxaliplatin) is a third generation platinum anticancer compound that produces the same type of interand intrastrand DNA cross-links as cisplatin. In combination with 5-fluorouracil, oxaliplatin has been recently approved in Europe, Asia, and Latin America for the treatment of metastatic colorectal cancer. We present here the crystal structure of an oxaliplatin adduct of a DNA dodecanucleotide duplex having the same sequence as that previously reported for cisplatin (Takahara, P. M.; Rosenzweig, A. C.; Frederick, C. A.; Lippard, S. J. Nature 1995, 377, 649-652). Pt-MAD data were used to solve this first X-ray structure of a platinated DNA duplex derived from an active platinum anticancer drug other than cisplatin. The overall geometry and crystal packing of the complex, refined to 2.4 Å resolution, are similar to that of the cisplatin structure, despite the fact that the two molecules crystallize in different space groups. The platinum atom of the {Pt(R,R-DACH)]2+ moiety forms a 1,2-intrastrand cross-link between two adjacent guanosine residues in

2 . 4 angstrom crystal structure of an oxaliplatin 1 , 2-d ( GpG ) intrastrand cross-link in a DNA dodecamer duplex