Comparative binding properties of metallobleomycins with DNA 10-mers

Properties of the interaction of bleomycin (Blm) and metallobleomycins [M Z n, Cu(LI), Fe(III), and HO2-Co(III)] with site-specific and nonspecific DNA oligomers, d(GGAAGCTTCC)(2) (I) and d(GGAAATTTCC)(2) (II), respectively, w ere investigated. With both 10-mers association constants increased in the series Blm A(2), ZnBlm A(2), Cu(II)Blm A(2), Fe(III)Blm A(2), and HO2-Co(II I)Blm A(2). Generally, the metallobleomycins were bound with a modestly hig her affinity to I. One-dimensional H-1 NMR spectra of the imino proton regi on of I in the presence of this series of compounds revealed that Blm and Z n- and CuBlm bind in fast exchange on the NMR time scale, while the Fe and Co complexes bind in slow exchange. Blm, ZnBlm, and Cu(II)Blm caused little perturbation of the UV circular dichroism spectrum of I or II, In contrast , Fe(m)Blm and HO2-Co(III)Blm induced hypochromic effects in the CD spectru m of I and altered the spectrum of II to a smaller extent. On the basis of these results, the DNA binding structures and properties of Blm A(2), ZnBlm A(2), and CuBlm A(2) differ substantially from those of Fe(m)Blm A(2) and HO2-Co(III)Blm A(2).