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一种β-折叠结构相互作用肽,可将细胞内蛋白质递送至人多能干细胞及其衍生物中。

A β-sheet structure interacting peptide for intracellular protein delivery into human pluripotent stem cells and their derivatives.

机构信息

Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos #04-01, 138669 Singapore, Singapore.

出版信息

Biochem Biophys Res Commun. 2012 May 11;421(3):616-20. doi: 10.1016/j.bbrc.2012.04.056. Epub 2012 Apr 19.

Abstract

The advance in stem cell research relies largely on the efficiency and biocompatibility of technologies used to manipulate stem cells. In our previous study, we had designed an amphipathic peptide RV24 that can deliver proteins into cancer cell lines efficiently without significant side effects. Encouraged by this observation, we moved forward to test whether RV24 could be used to deliver proteins into human embryonic stem cells and human induced pluripotent stem cells. RV24 successfully mediated protein delivery into these pluripotent stem cells, as well as their derivatives including neural stem cells and dendritic cells. Based on NMR studies and particle surface charge measurements, we proposed that hydrophobic domain of RV24 interacts with β-sheet structures of the proteins, followed by formation of "peptide cage" to facilitate delivery across cellular membrane. These findings suggest the feasibility of using amphipathic peptide to deliver functional proteins intracellularly for stem cell research.

摘要

干细胞研究的进展在很大程度上依赖于用于操纵干细胞的技术的效率和生物相容性。在我们之前的研究中,我们设计了一种两亲性肽 RV24,它可以有效地将蛋白质递送到癌细胞系中,而没有明显的副作用。受此观察结果的鼓舞,我们进一步测试了 RV24 是否可用于将蛋白质递送到人类胚胎干细胞和人类诱导多能干细胞中。RV24 成功地将蛋白质递送到这些多能干细胞及其衍生物中,包括神经干细胞和树突状细胞。基于 NMR 研究和颗粒表面电荷测量,我们提出 RV24 的疏水区与蛋白质的 β-折叠结构相互作用,随后形成“肽笼”以促进穿过细胞膜的输送。这些发现表明,使用两亲性肽将功能性蛋白质递送到细胞内用于干细胞研究是可行的。

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