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Comparative binding of antitumor drugs to DNA containing the telomere repeat sequence.
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2003-01-15 , DOI: 10.1038/emm.2002.46
Dongchul Suh 1 , Yu-Kyoung Oh , ByungChan Ahn , Man-Wook Hur , Hye-Ja Kim , Mi-Hyoung Lee , Hyo-Soon Joo , Chung- Kyoon Auh
Affiliation  

Telomeres are the ends of the linear chromosomes of eukaryotes and consist of tandem GT-rich repeats in telomere sequence i.e. 500-3000 repeats of 5'-TTAGGG-3' in human somatic cells, which are shortened gradually with age. The G-rich overhang of telomere sequence can adopt different intramolecular fold-backs and tetra-stranded DNA structures, in vitro, which inhibit telomerase activity. In this report, DNA binding agents to telomere sequence were studied novel therapeutic possibility to destabilize telomeric DNA sequences. Oligonucleotides containing the guanine repeats in human telomere sequence were synthesized and used for screening potential antitumor drugs. Telomeric DNA sequence was characterized using spectral measurements and CD spectroscopy. CD spectrum indicated that the double-stranded telomeric DNA is in a right-handed conformation. Polyacrylamide gel electrophoresis was performed for binding behaviors of antitumor compounds with telomeric DNA sequence. Drugs interacted with DNA sequence caused changes in the electrophoretic mobility and band intensity of the gels. Depending on the binding mode of the anticancer drugs, telomeric DNA sequence was differently recognized and the efficiency of cleavage of DNA varies in the bleomycin-treated samples under different conditions. DNA cleavage occurred at about 1% by the increments of 1 micromM bleomycin-Fe(III). These results imply that the stability of human telomere sequence is important in conjunction with the cancer treatment and aging process.

中文翻译:

抗肿瘤药物与包含端粒重复序列的DNA的比较结合。

端粒是真核生物线性染色体的末端,由端粒序列中富含GT的串联重复序列组成,即人类体细胞中5'-TTAGGG-3'的500-3000个重复序列,随着年龄的增长而逐渐缩短。端粒序列的富G突出端可以在体外采用不同的分子内折返和四链DNA结构,从而抑制端粒酶活性。在此报告中,研究了端粒序列的DNA结合剂使端粒DNA序列不稳定的新型治疗可能性。合成人端粒序列中含有鸟嘌呤重复序列的寡核苷酸,并将其用于筛选潜在的抗肿瘤药物。使用光谱测量和CD光谱法表征端粒DNA序列。CD谱表明双链端粒DNA处于右手构象。进行聚丙烯酰胺凝胶电泳以测定抗肿瘤化合物与端粒DNA序列的结合行为。与DNA序列相互作用的药物引起了凝胶电泳迁移率和谱带强度的变化。根据抗癌药的结合方式,端粒DNA序列被不同地识别,并且在不同条件下用博来霉素处理的样品中DNA的切割效率不同。通过1 micromM博来霉素-Fe(III)的增量,DNA切割发生率约为1%。这些结果表明,人类端粒序列的稳定性与癌症治疗和衰老过程有关。进行聚丙烯酰胺凝胶电泳以测定抗肿瘤化合物与端粒DNA序列的结合行为。与DNA序列相互作用的药物引起了凝胶电泳迁移率和谱带强度的变化。根据抗癌药的结合方式,端粒DNA序列被不同地识别,并且在不同条件下用博来霉素处理的样品中DNA的切割效率不同。通过1 micromM博来霉素-Fe(III)的增量,DNA切割发生率约为1%。这些结果表明,人类端粒序列的稳定性与癌症治疗和衰老过程有关。进行聚丙烯酰胺凝胶电泳以测定抗肿瘤化合物与端粒DNA序列的结合行为。与DNA序列相互作用的药物引起凝胶电泳迁移率和谱带强度的变化。根据抗癌药的结合方式,端粒DNA序列被不同地识别,并且在不同条件下用博来霉素处理的样品中DNA的切割效率不同。通过1 micromM博来霉素-Fe(III)的增量,DNA切割发生率约为1%。这些结果表明,人类端粒序列的稳定性与癌症治疗和衰老过程有关。根据抗癌药的结合方式,端粒DNA序列被不同地识别,并且在不同条件下用博来霉素处理的样品中DNA的切割效率不同。通过1 micromM博来霉素-Fe(III)的增量,DNA切割发生率约为1%。这些结果表明,人类端粒序列的稳定性与癌症治疗和衰老过程有关。根据抗癌药的结合方式,端粒DNA序列被不同地识别,并且在不同条件下用博来霉素处理的样品中DNA的切割效率不同。通过1 micromM博来霉素-Fe(III)的增量,DNA切割发生率约为1%。这些结果表明,人类端粒序列的稳定性与癌症治疗和衰老过程有关。
更新日期:2019-11-01
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