Backbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides.
Backbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides.
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DOI：
10.1038/ncomms1459
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发表时间：
2011-08-30
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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除了内吞介导的细胞摄取之外，亲水性细胞穿透肽能够以称为转导的非内吞模式穿过生物膜，导致立即的生物利用度。在这里，我们分析了结构要求的非内吞摄取模式的富含精氨酸的细胞穿透肽，通过活细胞显微镜，分子动力学模拟和分析ultracentrapgation相结合。我们证明了富含精氨酸的肽的转导效率随着肽结构刚性的增加而增加。因此，环状富含精氨酸的细胞穿透肽相对于其线性和更灵活的对应物显示出增强的细胞摄取动力学。我们建议，胍基团被迫到最远的位置通过环化。这种取向增加了膜接触，导致增强的细胞渗透。 穿膜肽能将分子物质送入活细胞，并通过非内吞机制转导穿过生物膜。在此，环状富含精氨酸的肽的转导效率显示出高于更柔性的线性肽的转导效率。
In addition to endocytosis-mediated cellular uptake, hydrophilic cell-penetrating peptides are able to traverse biological membranes in a non-endocytic mode termed transduction, resulting in immediate bioavailability. Here we analysed structural requirements for the non-endocytic uptake mode of arginine-rich cell-penetrating peptides, by a combination of live-cell microscopy, molecular dynamics simulations and analytical ultracentrifugation. We demonstrate that the transduction efficiency of arginine-rich peptides increases with higher peptide structural rigidity. Consequently, cyclic arginine-rich cell-penetrating peptides showed enhanced cellular uptake kinetics relative to their linear and more flexible counterpart. We propose that guanidinium groups are forced into maximally distant positions by cyclization. This orientation increases membrane contacts leading to enhanced cell penetration. Cell-penetrating peptides can deliver molecular cargoes into living cells, and cross biological membranes by transduction—a non-endocytic mechanism. Here, the transduction efficiency of cyclic arginine-rich peptides is shown to be higher than that of more flexible linear peptides.
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影响因子：
4.8
作者：
Palm-Apergi, Caroline;Lorents, Annely;Hallbrink, Mattias
通讯作者：
Hallbrink, Mattias
影响因子：
15
作者：
Rothbard, JB;Jessop, TC;Wender, PA
通讯作者：
Wender, PA
影响因子：
4.8
作者：
Tuennemann, Gisela;Martin, Robert M.;Cardoso, M. Cristina
通讯作者：
Cardoso, M. Cristina
DOI：
10.1073/pnas.91.2.664
发表时间：
1994-01-18
影响因子：
11.1
作者：
FAWELL, S;SEERY, J;BARSOUM, J
通讯作者：
BARSOUM, J
DOI：
10.1074/jbc.m805550200
发表时间：
2009-02-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ter-Avetisyan G;Tünnemann G;Nowak D;Nitschke M;Herrmann A;Drab M;Cardoso MC
通讯作者：
Cardoso MC