Abstract
Human Topoisomerase I (hTopo I) have been known as a potential target for cancer therapy. A series of duplex DNA with different intrinsic curvatures have been designed as inhibitors to hTopo I. The activities of hTopo I on relaxing supercoiled plasmid pUC 19 are apparently diminished in the presence of the curved DNA. More potent inhibitions and smaller IC(50) are achieved by duplex DNA with higher curvatures. EMSA indicates that hTopo I can recognize the curved DNA through binding interactions. Our studies demonstrate that the activity of hTopo I can be modulated by the intrinsic curvature of linear DNA and provide a new avenue to design curved DNA as hTopo I inhibitors with high therapeutic efficiency and low toxicity.
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