Cellular Translocation of a γ-AApeptide Mimetic of Tat Peptide
Cellular Translocation of a γ-AApeptide Mimetic of Tat Peptide
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DOI：
10.1021/mp300070w
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发表时间：
2012-05-01
影响因子：
4.9
通讯作者：
Cai, Jianfeng
中科院分区：
文献类型：
--
作者：
Niu, Youhong;Bai, Ge;Cai, Jianfeng
细胞穿透肽包括来自HIV-1的反式激活转录激活因子（Tat）已被用作细胞内递送无数货物的载体，包括药物、分子探针、dna和纳米颗粒。利用荧光流式细胞术和共聚焦荧光显微镜，我们证明了Tat（48-57）的γ - aapeptant可以穿过细胞膜进入细胞质和细胞核，其效率与Tat肽（48-57）相当或更好。γ - a肽的四个侧链的缺失减弱了易位能力。我们还证实，γ - a肽对哺乳动物细胞的毒性甚至比Tat肽更小。除了它们的低毒性外，γ - a- apeptides抵抗蛋白酶降解，这可能被证明比α -peptide更有利于进一步开发用于细胞内递送的分子转运体。
Cell-penetrating peptides including the trans-activating transcriptional activator (Tat) from HIV-1 have been used as carriers for intracellular delivery of a myriad of cargoes including drugs, molecular probes, DNAs and nanoparticles. Utilizing fluorescence flow cytometry and confocal fluorescence microscopy, we demonstrate that a gamma-AApeptide mimetic of Tat (48-57) can cross the cell membranes and enter the cytoplasm and nucleus of cells, with efficiency comparable to or better than that of Tat peptide (48-57). Deletion of the four side chains of the gamma-AApeptide attenuates translocation capability. We also establish that the gamma-AApeptide is even less toxic than the Tat peptide against mammalian cells. In addition to their low toxicity, gamma-AApeptides are resistant to protease degradation, which may prove to be advantageous over alpha-peptides for further development of molecular transporters for intracellular delivery.