摘要
酪氨酸-DNA磷酸二酯酶Ⅰ(tyrosyl-DNA-phosphodiesteraseⅠ,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(topoisomeraseⅠ,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。
Tyrosyl-DNA phosphodiesterase I （Tdp I ） 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 （Top I ）. Tdp I has been regarded as a potential therapeutic co-target of Top I because it has the functions of repairing Top I compound and counteracting the effects of Top I inhibitors. Tdp I inhibitors can not only synergizing with Top I -targeting drugs （camptotbecins）, but also strength the function of bleomycin, topoisomerase II （Top II ） inhibitors （etoposide, doxorubicin） and DNA alkylating agents. We summarized the researching advance of Tdp I inhibitors and focused on the introduction of the mecha nism, bioactivity and structure-activity relationship.
出处
《药学实践杂志》
CAS
2015年第4期298-308,379,共12页
Journal of Pharmaceutical Practice
基金
国家优秀青年科学基金(No.81222044)
