DNA cleavage by novel copper (II) complex and the role of beta-cyclodextrin in promoting cleavage.
A new cyclen derivative N-1-naphthyl-[4-amino-5-oxo-5-(1,4,7,10-tetraazacyclododecan-1-yl)]valeramide and the copper (II) complex were synthesized and characterized. The copper (II) complex showed DNA cleavage ability without the existence of other additives. The pUC19 plasmid DNA was cleaved to linear form by 0.71 microM of complex under physiological conditions. beta-Cyclodextrin was used to investigate the relationship of nuclease activity and DNA binding ability. The addition of beta-cyclodextrin exhibited an unexpected ability to promote the cleavage of DNA. The role of the beta-cyclodextrin in DNA cleavage process was studied by (1)H NMR and fluorescence spectrum. According to the data of viscosity measurement, it was confirmed that the binding of complex with DNA should be a groove binding model. All the results suggested that the increasing of the DNA cleavage ability was attributed to the interaction between beta-cyclodextrin and the naphthyl moieties. beta-Cyclodextrin could include the naphthyl moieties and keep it from the minor/major groove of DNA and decreased the DNA binding ability, therefore, the copper (II) center was activated to generate more reactive oxygen species, which was responsible for DNA cleavage.
Huang
Yu
Y
Department of Chemistry, Key Laboratory of Green Chemistry and Technology (Ministry of Education), Sichuan University, Chengdu 610064, PR China.
Lu
Qiao-Sen
QS
Zhang
Ji
J
Zhang
Zhong-Wei
ZW
Zhang
Yu
Y
Chen
Shan-Yong
SY
Li
Kun
K
Tan
Xin-Yu
XY
Lin
Hong-Hui
HH
Yu
Xiao-Qi
XQ
D003300:Copper / Q000737:chemistry*; D053837:DNA Cleavage; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010957:Plasmids / Q000235:genetics; D013050:Spectrometry, Fluorescence; D017186:Titrimetry; D047392:beta-Cyclodextrins / Q000737:chemistry*
D047392:beta-Cyclodextrins; D003300:Copper; C031215:betadex