title: Fe- and Co-bleomycins bound to site specific and nonspecific DNA decamers: comparative binding and reactivity of their metal centers.
abstract: Co- and Fe-bleomycins (Blms) have been reacted with DNAa, d(GGAAGCTTCC)2, containing a specific site for cleavage, and DNAb, d(GGAAATTTCC)2, a closely related nonspecific 10-mer, to survey whether features of structure and reactivity of these adducts vary systematically as a function of the base sequence of the DNA oligomer. The ESR spectrum of NO-Fe(II)BlmDNAa is rhombically perturbed in comparison with that of NO-Fe(II)BlmDNAb, which is nearly identical to the spectrum of NO-Fe(II)Blm. The ESR spectrum of Fe(III)BlmDNAa in phosphate buffer is low-spin; that of Fe(III)BlmDNAb is high-spin as seen with Fe(III)Blm alone. According to absorbance spectroscopy, O2-Fe(II)BlmDNAa is stabilized in comparison with the DNAb adduct. Similar stabilization of O2-Co(II)Blm bound to DNAa but not to DNAb was also observed by ESR spectroscopy. HO2(-)-Co(III)Blm A2 binds in slow exchange on the NMR time scale to DNAa at its 5'-G-pyrimidine-3' site of cleavage. In contrast, fluorescence and NMR spectroscopy demonstrate that most of HO2(-)-Co(III)Blm A2 binds stoichiometrically in fast exchange to DNAb. The reactions of Fe(III)BlmDNAa and Fe(III)BlmDNAb with ascorbate and O2 reveal that the latter becomes activated and cleaves its 10-mer, producing base propenals, at a faster initial rate. Thus, in two series of metallobleomycins, (A) NO-Fe(II)Blm, O2-Fe(II)Blm, Fe(III)Blm in phosphate buffer, and HO2(-)-Fe(III)Blm and (B) O2-Co(II)Blm and HO2(-)-Co(III)Blm, the metal domain of each species interacts differently with DNA depending upon its base sequence.
authors.affiliation: Department of Chemistry, University of Wisconsin-Milwaukee, 53211, USA.
authors.forename: P
authors.initials: P
authors.lastname: Fulmer
authors.forename: C
authors.initials: C
authors.lastname: Zhao
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: E
authors.initials: E
authors.lastname: DeRose
authors.forename: W E
authors.initials: WE
authors.lastname: Antholine
authors.forename: D H
authors.initials: DH
authors.lastname: Petering
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D003035:Cobalt / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry
chemical_list: D000903:Antibiotics, Antineoplastic; D018736:DNA Adducts; D009838:Oligodeoxyribonucleotides; D010545:Peroxides; C030187:cobalt bleomycin; C023503:iron bleomycin; D001761:Bleomycin; D003035:Cobalt; D004247:DNA; D007501:Iron; D001205:Ascorbic Acid