Arimondo P, Bailly C, Boutorine A, Asseline U, Sun J S, Garestier T, Hélène C
Laboratoire de Biophysique, UMR 8646 CNRS-Muséum National d'Histoire Naturelle, INSERM U201, Paris, France.
Nucleosides Nucleotides Nucleic Acids. 2000 Aug;19(8):1205-18. doi: 10.1080/15257770008033044.
Amsacrine-4-carboxamide-oligonucleotide conjugates were synthesized and studied for their capacity to form DNA triple helices and to alter human topoisomerase II binding and cleavage properties. The intercalating agent was attached to the 3'- or the 5'-end of a 24 nt triple helix-forming oligonucleotide via linkers of different lengths. The stability of these DNA triple helices was investigated by gel retardation and melting temperature studies using a synthetic 70 bp DNA duplex target. The effect of the conjugates on DNA cleavage by topoisomerase II was evaluated using the 70 bp duplex and a 311 bp restriction fragment containing the same triple helix site. The conjugate with the amsacrine derivative linked to the 3' end of the TFO via a hexaethylene glycol linker modulates the extent of DNA cleavage by topoisomerase II at specific sites.
合成了氨吖啶 - 4 - 羧酰胺 - 寡核苷酸缀合物，并研究了它们形成DNA三链螺旋以及改变人类拓扑异构酶II结合和切割特性的能力。嵌入剂通过不同长度的接头连接到24个核苷酸的三链螺旋形成寡核苷酸的3'端或5'端。使用合成的70 bp DNA双链体靶标，通过凝胶阻滞和熔解温度研究来研究这些DNA三链螺旋的稳定性。使用70 bp双链体和包含相同三链螺旋位点的311 bp限制性片段评估缀合物对拓扑异构酶II切割DNA的影响。通过六甘醇接头连接到TFO 3'端的氨吖啶衍生物缀合物可调节拓扑异构酶II在特定位点切割DNA的程度。
