Repozytorium
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Inne
Phleomycin complex : coordination mode and in vitro cleavage of DNA.
Autorzy
Rok wydania
2019
Czasopismo
Journal of Inorganic Biochemistry
Numer woluminu
195
Strony
71-82
DOI
10.1016/j.jinorgbio.2019.03.010
Kolekcja
Język
Angielski
Typ publikacji
Artykuł
Phleomycin is one of the anticancer glycopeptide antibiotics which cause DNA cleavage. It is commonly used as a copper(II) complex. Therefore, it is important to study the metal ion binding process and to define the coordination mode. In this paper, we describe the acid-base properties of phleomycin and the coordination sphere of the Cu(II) cation. In the metal binding process up to five nitrogen donor atoms can be involved. Four of them in the same plane deriving from: the pyrimidine ring, secondary amine of β-aminoalanine, imidazole and amide of the nearest peptide bond (from β-hydroxyhistidine) and in the apical position from the α-amino functional group of β-aminoalanine, resulting complex has a square-pyramidal geometry. Phleomycin complexes are able to induce single- and double-stranded DNA damage when they are accompanied by one-electron reductants, such as dithiothreitol, glutathione, 2-mercaptoethanol or ascorbic acid. In such conditions they produce reactive oxygen species which are responsible for DNA cleavage. The metal ion binding site is relatively close to the nucleic acid interacting moiety. This supports the hypothesis that copper ion is important in the anticancer activity which involves DNA degradation.
Adres publiczny
http://dx.doi.org/10.1016/j.jinorgbio.2019.03.010
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