Abstract
Proton NMR spectra demonstrate the formation of a ternary complex, Zn(II)--bleomycin-A2--poly(dA-dT), which serves as an analog of the putative active complex, Fe(II)--bleomycin-A2--DNA. Specific sites of metal--drug and drug--nucleic acid interaction have been delineated on the basis of chemical shift perturbations. On the basis of this criterion there appear to be three distinct regions of the drug: (i) the NH2 terminus up to and including the disaccharide and hydroxyhistidine residues, whose resonances are perturbed only by metal interactions; (ii) the COOH-terminal dipeptide, whose resonances are displaced only by nucleic acid interactions; and (iii) the methylvaleric acid-threonine dipeptide, which links these domains and whose resonances are sensitive to both types of interactions. The spectral perturbations in the first and second domains are very similar to changes observed in the corresponding binary complexes--i.e., Zn(II)--bleomycin-A2 and bleomycin-A2--poly(dA-dT), respectively.
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