| 酪氨酸-DNA磷酸二酯酶抑制剂的研究进展 |
| 投稿时间：2014-07-14 修订日期：2014-10-27 点此下载全文 |
| 引用本文：黄亚辉,董国强,张万年,盛春泉.酪氨酸-DNA磷酸二酯酶抑制剂的研究进展[J].药学实践杂志,2015,33(4):298~302 |
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| 基金项目:国家优秀青年科学基金(No.81222044) |
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| 中文摘要:酪氨酸-DNA磷酸二酯酶Ⅰ(tyrosyl-DNA-phosphodiesterase Ⅰ,TdpⅠ)是一个具有催化3'磷酸酪氨酸键水解活性的蛋白质,该键在拓扑异构酶Ⅰ(topoisomerase Ⅰ, TopⅠ)与DNA相互作用时就会形成。由于TdpⅠ具有修复TopⅠ-DNA复合物、抵消TopⅠ抑制剂作用的功能,因而与TopⅠ共同被认作是潜在治疗靶标。TdpⅠ抑制剂不仅与TopⅠ抑制剂(喜树碱类)起到协同作用,还能增强博来霉素、TopⅡ抑制剂(依托泊苷、多柔比星)以及DNA烷化剂作用。综述目前报道的TdpⅠ抑制剂研究进展,重点介绍其作用机制、生物活性及构效关系。 |
| 中文关键词:酪氨酸-DNA磷酸二酯酶Ⅰ(TdpⅠ) 拓扑异构酶Ⅰ(TopⅠ) 抗肿瘤药物 构效关系 |
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| Recent advances of tyrosyl-DNA phosdiesterase Ⅰ (TdpⅠ) inhibitors |
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| Abstract:Tyrosyl-DNA phosphodiesterase Ⅰ (TdpⅠ) is a recently discovered proteinthat catalyzes the hydrolysis of 3'-phosphotyrosyl bonds. Such linkages form in vivo during the interaction of DNA and topoisomerase Ⅰ (TopⅠ). TdpⅠ has been regarded as a potential therapeutic co-target of TopⅠ because it has the functions of repairing TopⅠ compound and counteracting the effects of TopⅠ inhibitors. TdpⅠ inhibitors can not only synergizing with TopⅠ-targeting drugs (camptothecins), but also strength the function of bleomycin, topoisomerase Ⅱ (TopⅡ) inhibitors (etoposide, doxorubicin) and DNA alkylating agents. We summarized the researching advance of TdpⅠ inhibitors and focused on the introduction of the mechanism, bioactivity and structure-activity relationship. |
| keywords:tyrosyl-DNA phosphodiesterase Ⅰ (TdpⅠ) topoisomerase Ⅰ (TopⅠ) anti-tumor inhibitors structure and activity relationship |
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