肽
亚细胞定位
细胞生物学
功能(生物学)
体外
生物化学
生物
计算生物学
合成生物学
化学
细胞质
作者
G.G. Rhys,Jessica A. Cross,William M. Dawson,Harry Thompson,S. Shanmugaratnam,Nigel J. Savery,Mark P. Dodding,Birte Höcker,Derek N. Woolfson
标识
DOI:10.1038/s41589-022-01076-6
摘要
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. The de novo design of a pair of complementary peptides, one basic for cell penetration and target binding and one acidic that can be fused to proteins of interest, provides an approach for delivery into mammalian cells and subcellular targeting.
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