TY - JOUR
T1 - Interaction of the antitumour antibiotic streptonigrin with DNA and oligonucleotides
AU - Long, Georgina V.
AU - Harding, Margaret M.
AU - Fan, Jun Yao
AU - Denny, William A.
PY - 1997/9
Y1 - 1997/9
N2 - The interaction of the aminoquinone antitumour antibiotic streptonigrin with plasmid DNA, calf thymus DNA and oligonucleotides, in the presence and absence of metal ions, has been studied using circular dichroism, NMR spectroscopy and gel electrophoresis experiments. In the absence of metal ions, streptonigrin does not interact with DNA. Incubation of the two enantiomers of streptonigrin with calf thymus DNA, in the presence of excess zinc(II), showed no evidence of selective interaction of the natural enantiomer, (R)-streptonigrin, with the DNA by circular dichroism. The interaction of streptonigrin with the hexanucleotide d(GCATGC)2 was studied by 1H- and 31P-NMR spectroscopy. In the presence of four equivalents of zinc(II) nitrate and one equivalent of streptonigrin, small changes in chemical shifts of the proton resonances associated with T4 and G5 were detected as well as P4 and P5, consistent with a weak interaction of the zinc(II)-streptonigrin complex with the most accessible binding sites, involving the phosphate groups and guanine N7, at either end of the duplex. In contrast, no significant interaction between the metal complex and d(ATGCAT)2 was detected. Gel electrophoresis experiments were carried out to probe the sequence specificity of the interaction of the non-covalent streptonigrin-metal complexes with DNA, the DNA cleavage reaction of supercoiled DNA, and the specificity of the cleavage reaction. DNase I footprinting showed no sequence specific interactions. Zinc(II), copper(II) and manganese(II) enhanced the cleavage of supercoiled DNA into nicked and linear forms of DNA, while magnesium showed no cleavage reactions under identical conditions. The DNA cleavage reaction of streptonigrin and NADH in the presence and absence of metal ions was studied. Overall, little sequence specificity was observed, but slightly different cleavage patterns suggest that the DNA cleavage can be influenced by the nature of the metal ions.
AB - The interaction of the aminoquinone antitumour antibiotic streptonigrin with plasmid DNA, calf thymus DNA and oligonucleotides, in the presence and absence of metal ions, has been studied using circular dichroism, NMR spectroscopy and gel electrophoresis experiments. In the absence of metal ions, streptonigrin does not interact with DNA. Incubation of the two enantiomers of streptonigrin with calf thymus DNA, in the presence of excess zinc(II), showed no evidence of selective interaction of the natural enantiomer, (R)-streptonigrin, with the DNA by circular dichroism. The interaction of streptonigrin with the hexanucleotide d(GCATGC)2 was studied by 1H- and 31P-NMR spectroscopy. In the presence of four equivalents of zinc(II) nitrate and one equivalent of streptonigrin, small changes in chemical shifts of the proton resonances associated with T4 and G5 were detected as well as P4 and P5, consistent with a weak interaction of the zinc(II)-streptonigrin complex with the most accessible binding sites, involving the phosphate groups and guanine N7, at either end of the duplex. In contrast, no significant interaction between the metal complex and d(ATGCAT)2 was detected. Gel electrophoresis experiments were carried out to probe the sequence specificity of the interaction of the non-covalent streptonigrin-metal complexes with DNA, the DNA cleavage reaction of supercoiled DNA, and the specificity of the cleavage reaction. DNase I footprinting showed no sequence specific interactions. Zinc(II), copper(II) and manganese(II) enhanced the cleavage of supercoiled DNA into nicked and linear forms of DNA, while magnesium showed no cleavage reactions under identical conditions. The DNA cleavage reaction of streptonigrin and NADH in the presence and absence of metal ions was studied. Overall, little sequence specificity was observed, but slightly different cleavage patterns suggest that the DNA cleavage can be influenced by the nature of the metal ions.
KW - Antitumor antibiotic
KW - DNA cleavage
KW - Drug-oligonucleotide complex
KW - Footprinting
KW - Streptonigrin
UR - http://www.scopus.com/inward/record.url?scp=8544236988&partnerID=8YFLogxK
M3 - Article
SN - 0266-9536
VL - 12
SP - 453
EP - 472
JO - Anti-Cancer Drug Design
JF - Anti-Cancer Drug Design
IS - 6
ER -