Comparative binding properties of metallobleomycins with DNA 10-mers.
Properties of the interaction of bleomycin (Blm) and metallobleomycins [M = Zn, Cu(II), Fe(III), and HO(2)-Co(III)] with site-specific and nonspecific DNA oligomers, d(GGAAGCTTCC)(2) (I) and d(GGAAATTTCC)(2) (II), respectively, were 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 HO(2)-Co(III)Blm A(2). Generally, the metallobleomycins were bound with a modestly higher affinity to I. One-dimensional (1)H NMR spectra of the imino proton region of I in the presence of this series of compounds revealed that Blm and Zn- 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(III)Blm and HO(2)-Co(III)Blm induced hypochromic effects in the CD spectrum 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(III)Blm A(2) and HO(2)-Co(III)Blm A(2).
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Department of Chemistry, University of Wisconsin-Milwaukee, P.O. Box 413, Milwaukee, Wisconsin 53201, USA.
Zhao
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Xia
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Antholine
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Petering
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D001665:Binding Sites; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000737:chemistry*; D002942:Circular Dichroism; D003035:Cobalt / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry*; D007501:Iron / Q000737:chemistry; D008670:Metals / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D015032:Zinc / Q000737:chemistry
D018736:DNA Adducts; D008670:Metals; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; C023502:copper bleomycin; C023503:iron bleomycin; C085742:peroxycobalt bleomycin; C099533:zinc bleomycin; D001761:Bleomycin; D003035:Cobalt; D003300:Copper; D007501:Iron; D015032:Zinc