Faculty Collaboration Database

Fe- and Co-bleomycins bound to site specific and nonspecific DNA decamers: comparative binding and reactivity of their metal centers. Biochemistry 1997 Apr 08;36(14):4367-74

Date

04/08/1997

Pubmed ID

9100034

DOI

10.1021/bi9625354

Scopus ID

2-s2.0-0030981907 (requires institutional sign-in at Scopus site)   32 Citations

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.

Author List

Fulmer P, Zhao C, Li W, DeRose E, Antholine WE, Petering DH

MESH terms used to index this publication - Major topics in bold

Antibiotics, Antineoplastic
Ascorbic Acid
Bleomycin
Cobalt
DNA
DNA Adducts
Electron Spin Resonance Spectroscopy
Iron
Magnetic Resonance Spectroscopy
Molecular Structure
Nucleic Acid Conformation
Oligodeoxyribonucleotides
Peroxides
Spectrometry, Fluorescence
Spectrophotometry