Acylation of octaarginine: Implication to the use of intracellular delivery vectors
Acylation of octaarginine: Implication to the use of intracellular delivery vectors
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DOI：
10.1016/j.jconrel.2010.02.004
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发表时间：
2011-01-05
影响因子：
10.8
通讯作者：
Futaki, Shiroh
中科院分区：
文献类型：
--
作者：
Katayama, Sayaka;Hirose, Hisaaki;Futaki, Shiroh
细胞穿透肽（CPP）具有有效地内化到细胞中的能力，因此已被用作用于细胞内递送各种生物活性分子的载体。将疏水核心引入CPP可以增加它们与膜的相互作用并促进它们移位到细胞中。虽然已经大量报道了酰化寡精氨酸对基因和siRNA递送的有用性，但是关于它们用于递送小分子量化合物、肽和蛋白质的信息很少。在这份报告中，我们采用八精氨酸（R8）作为一个典型的富含精氨酸的CPP和评估的影响，使用丁酸，己酸和癸酸的酰化能力作为一个交付载体。己酰基八精氨酸（C6 R8-Alexa）显示出所研究变体的最高细胞摄取效率，比R8-Alexa高十倍。C6 R8-Alexa也产生弥散的胞质分布。另一方面，对于蛋白质的递送，观察到C6 R8相对于R8的不太显著的效果，这表明在相对小分子量化合物的递送期间可以获得C6 R8的优势。尽管没有37摄氏度时那么明显。在4 ℃下观察到C6 R8-Alexa的显著胞质分布。这表明C6 R8肽直接穿透质膜的潜在能力。(C)2010 Elsevier B. V.保留所有权利。
Cell-penetrating peptides (CPPs) have the ability to efficiently internalize into cells and thus have been used as a vector for the intracellular delivery of various bioactive molecules. The introduction of a hydrophobic core to CPPs may increase their interaction with membranes and facilitate their translocation into cells. While the usefulness of acylated oligoarginine to gene and siRNA delivery has been largely reported, little information is available about their use for the delivery of small molecular-weight compounds, peptides and proteins. In this report, we employed octaarginine (R8) as a typical arginine-rich CPP and evaluated the effect of acylation using butanoic, hexanoic and decanoic acids on its capacity as a delivery vector. Hexanoyl octaarginine (C6R8-Alexa) showed the highest efficiency of cellular uptake of the studied variants, ten times higher than R8-Alexa. C6R8-Alexa also produced a diffuse cytosolic distribution. On the other hand, a less significant effect of C6R8 over R8 was observed for the delivery of proteins, suggesting that the advantage of C6R8 may be obtained during the delivery of relatively small molecular-weight compounds. Although less prominent than at 37 degrees C. a significant cytosolic distribution of C6R8-Alexa was observed at 4 degrees C. and this suggested the potential ability of the C6R8 peptide for direct penetration through plasma membranes. (C) 2010 Elsevier B.V. All rights reserved.