Influence of lysine residue in amphipathic helical peptides on targeted delivery of RNA into cancer cells
Influence of lysine residue in amphipathic helical peptides on targeted delivery of RNA into cancer cells
复制标题
两亲性螺旋肽中赖氨酸残基对 RNA 靶向递送至癌细胞的影响
DOI：
10.1016/j.bmcl.2019.05.044
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发表时间：
2019
影响因子：
2.7
通讯作者：
Urata Hidehito
中科院分区：
文献类型：
--
作者：
Wada Shun-ichi;Taniguchi Kohei;Hamazaki Hiroaki;Yamada Azusa;Hayashi Junsuke;Uchiyama Kazuhisa;Urata Hidehito
已报道cRGD缀合的含Aib的两亲性螺旋肽MAP（Aib）衍生物（PI）是用于siRNA递送到细胞中的有用载体。我们进行了一系列的构效关系研究，研究了疏水性和碱性之间的平衡对PI两亲性的影响，并合成了比PI具有更多赖氨酸残基的肽。增加两亲性螺旋中碱性残基的数量抑制了将siRNA递送到细胞中的能力。因此，PI螺旋中疏水性和碱性之间的平衡对于siRNA进入细胞是重要的。此外，PI的siRNA递送能力对癌细胞如A549、U-87 MG和WiDr细胞具有特异性，而对正常细胞即NIH 3 T3细胞的siRNA递送能力较低。接下来，我们检查了PI作为递送microRNA-133 b（miR-133 b）的载体的潜力，所述microRNA-133 b（miR-133 b）已知是抗肿瘤iR 13 PI增强miR-133 b向WiDr细胞中的递送，这导致内源性蛋白表达的抑制。
The cRGD-conjugated Aib-containing amphipathic helical peptide, MAP(Aib) derivative (PI), has been reported to be a useful carrier for siRNA delivery into cells. We have conducted a series of structure-activity relationship studies of the influence of the balance between hydrophobicity and basicity on the amphipathicity ofPI, and synthesized peptides having a larger number of Lys residues thanPI. Increasing the number of basic residues in the amphipathic helix suppressed the ability to deliver siRNA into cells. It was concluded that the balance between hydrophobicity and basicity in thePIhelix was important for siRNA delivery into cells. Furthermore, the siRNA delivering ability ofPIwas specific to cancer cells, such as A549, U-87 MG, and WiDr cells, and was low in normal cells, namely, NIH3T3 cells. Next, we examined the potential ofPIas a carrier for the delivery of microRNA-133b (miR-133b), which is known to be an anti-oncomiR.PIenhanced the delivery of miR-133b into WiDr cells, which resulted in the suppression of endogenous protein expression.