Enhanced intracellular delivery using arginine-rich peptides by the addition of penetration accelerating sequences (Pas)

Enhanced intracellular delivery using arginine-rich peptides by the addition of penetration accelerating sequences (Pas)
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DOI:
10.1016/j.jconrel.2009.05.019
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发表时间:
2009-09-01
影响因子:
10.8
通讯作者:
Futaki, Shiroh
Futaki, Shiroh
中科院分区:
医学1区
文献类型:
--
作者:
Takayama, Kentaro;Nakase, Ikuhiko;Futaki, Shiroh

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细胞穿透肽(CPP),包括富含精氨酸的肽,是用于具有低膜渗透性的各种生物活性分子的细胞内递送的有吸引力的工具。我们表明,通过向富含精氨酸的CPP中加入短肽段(渗透加速序列,Pas),可以实现富含精氨酸的肽的加速细胞内递送。即使在血清存在下,在用肽处理细胞后5分钟内也观察到PAS附着的富含精氨酸的CPP的胞质释放。Pas区段在使用富含精氨酸的CPP的生物活性肽的细胞内递送中的有效性通过由源自p53 C-末端22-氨基酸区段(位置361-382)的反转肽增强的恶性神经胶质瘤细胞的生长抑制活性来举例说明。All rights reserved. (C)2009爱思唯尔有限公司版权所有。
Cell penetrating peptides (CPPs), including arginine-rich peptides, are attractive tools for the intracellular delivery of various bioactive molecules with a low membrane permeability. We showed that the accelerated intracellular delivery of arginine-rich peptides was achieved by the addition of a short peptide segment (penetration accelerating sequence, Pas) to arginine-rich CPPs. The cytosolic release of the Pas-attached arginine-rich CPPs was observed within 5 min after the treatment of the cells with the peptides even in the presence of serum. Effectiveness of the Pas segment in the intracellular delivery of bioactive peptides using arginine-rich CPPs was exemplified through the enhanced growth inhibition activity of the malignant glioma cells by a retro-inverso peptide derived from the p53 C-terminal 22-amino-acid segment (positions 361-382). All rights reserved. (C) 2009 Elsevier B.V. All rights reserved.