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白蛋白结合肽-多柔比星耦合物的设计、制备、表征及初步评价
Authors
余蓉
刘永东
+6 more
刘立平
张纯
张耀
殷爽
王祺
苏志国
Publication date
1 January 2017
Publisher
Abstract
为了改善多柔比星在血液中的循环半衰期,基于白蛋白在血浆中含量丰富、性质稳定、半衰期持久的特点,通过大肠杆菌体系重组表达了源于细菌表面蛋白中白蛋白结合肽段,并建立了纯化工艺,获得了纯度高于95%的重组白蛋白结合多肽,并证明重组多肽在体外能够迅速地与人血清白蛋白结合。通过与DOXO-EMCH分子化学耦联,制备获得重组白蛋白结合肽-多柔比星耦合物。A549细胞毒力实验结果显示耦合物的IC50浓度升高,药代动力学结果显示重组白蛋白结合肽能够显著延长多柔比星在血液中的循环半衰期,相对于多柔比星或DOXO-EMCH分别提高了5.6倍和3.8倍。荷瘤小鼠肿瘤生长抑制实验结果显示耦合物的抗肿瘤效力得到提升。证明了基于白蛋白结合机制可为小分子药物长效设计提供新的思路。</p
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Institutional Repository of Institute of Process Engineering, CAS (IPE-IR)
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oai:ir.ipe.ac.cn:122111/33508
Last time updated on 05/12/2019
Institutional Repository of Institute of Process Engineering, CAS (IPE-IR)
See this paper in CORE
Go to the repository landing page
Download from data provider
oai:ir.ipe.ac.cn:122111/25263
Last time updated on 08/09/2018