De novo designed peptides for cellular delivery and subcellular localisation.
De novo designed peptides for cellular delivery and subcellular localisation.
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从头设计用于细胞递送和亚细胞定位的肽。
DOI：
10.1038/s41589-022-01076-6
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发表时间：
2022
影响因子：
14.8
通讯作者：
Rhys GG
中科院分区：
文献类型：
--
作者：
Rhys GG
从第一原理或计算上重新设计肽和蛋白质组装体的可能性越来越大。这种方法为功能性合成多肽提供了新的途径，包括靶向和结合感兴趣的蛋白质的设计。这项工作大部分是在体外进行的。因此，挑战是将从头多肽有效地递送至细胞内的作用位点。在这里，我们描述了从头合成肽系统的设计，表征，细胞内交付，和亚细胞定位。该系统包括双功能碱性肽和互补酸性肽，所述双功能碱性肽被编程用于细胞穿透和靶结合，所述互补酸性肽可以与感兴趣的蛋白质融合并使用合成DNA引入细胞中。这些设计的特点是在体外使用生物物理方法和X射线晶体学。该系统用于递送到哺乳动物细胞和亚细胞靶向的实用性通过标记细胞器和主动接合功能蛋白质复合物来证明。
Increasingly, it is possible to design peptide and protein assemblies de novo from first principles or computationally. This approach provides new routes to functional synthetic polypeptides, including designs to target and bind proteins of interest. Much of this work has been developed in vitro. Therefore, a challenge is to deliver de novo polypeptides efficiently to sites of action within cells. Here we describe the design, characterisation, intracellular delivery, and subcellular localisation of a de novo synthetic peptide system. This system comprises a dual-function basic peptide, programmed both for cell penetration and target binding, and a complementary acidic peptide that can be fused to proteins of interest and introduced into cells using synthetic DNA. The designs are characterised in vitro using biophysical methods and X-ray crystallography. The utility of the system for delivery into mammalian cells and subcellular targeting is demonstrated by marking organelles and actively engaging functional protein complexes.