The solution structure of Co Bleomycin (CoBLM) A2 green (the hydroperoxide form of CoBLM) complexed with the self-complementary oligonucleotide d(CCAGGCCTGG) with a cleavage site at C6 has been determined by 2D NMR spectroscopic methods and molecular dynamics calculations. Intermolecular NOEs (60 between CoBLM A2 green and DNA) and intramolecular NOEs (61 within CoBLM A2 green) have defined the position and orientation of CoBLM A2 green with respect to its single binding site in the duplex. CoBLM A2 green is a stable analog of the activated BLM, the Fe3+ hydroperoxide (Sam, J. W.; Tang, X.-J.; Peisach, J. J. Ant. Chem. Sec. 1994, 116, 5250-5256). These studies have provided the first structural insight into the mode of binding of the bithiazole tail of CoBLM A2 green to DNA, the basis for specificity of its cleavage at pyrimidines (Py) in d(G-Py) sequences, and the orientation of its terminal oxygen of the hydroperoxide relative to the 4’ carbon hydrogen bond being cleaved in the DNA. The bithiazole tail inserts 3’ to the C6 cleavage site from the minor groove. The terminal thiazolium ring is completely stacked between the bases of G14 and G15, while the penultimate thiazolium ring is only partially stacked between the bases of C6 and C7.