Enhanced intracellular peptide delivery by multivalent cell-penetrating peptide with bioreducible linkage
Enhanced intracellular peptide delivery by multivalent cell-penetrating peptide with bioreducible linkage
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DOI：
10.1016/j.bmcl.2017.12.035
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发表时间：
2018-02-01
影响因子：
2.7
通讯作者：
Ohtsuki, Takashi
中科院分区：
文献类型：
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作者：
Kim, Hyungjin;Kitamatsu, Mizuki;Ohtsuki, Takashi
已报道多价细胞穿透肽（CPP）显示出细胞摄取和内体溶解活性的增强。然而，其应用仅限于货物的反式递送，其货物的细胞摄取效率低于顺式递送。在这里，我们尝试了通过使用TatBim肽制备具有凋亡活性的生物可还原的二聚CPP-货物来顺式递送具有多价CPP的货物，所述TatBim肽是达特CPP和衍生自Bim凋亡诱导蛋白的Bim肽的融合物。与单体TatBim相比，二聚体TatBim几乎是细胞内化的两倍，并显著诱导细胞凋亡。还证实了二聚体TatBim的生物可还原键对凋亡活性的贡献。(C)2017爱思唯尔有限公司版权所有
Multivalent cell-penetrating peptides (CPPs) have been reported to show enhancement in cellular uptake and endosomolytic activity. However, its application was limited to trans-delivery of cargo which is lower in cellular uptake efficiency of cargo than cis-delivery. Here, we tried the cis-delivery of cargo with multivalent CPP by preparing bioreducible dimeric CPP-cargo with apoptotic activity using TatBim peptide, a fusion of Tat CPP and Bim peptide derived from Bim apoptosis-inducing protein. Dimeric TatBim was almost twice as highly internalized by cells and significantly induced apoptosis compared to monomeric TatBim. Contribution of bioreducible linkage of dimeric TatBim towards apoptotic activity was also confirmed. (C) 2017 Elsevier Ltd. All rights reserved.