7q1r

Publication Abstract from PubMed

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.

De novo designed peptides for cellular delivery and subcellular localisation.,Rhys GG, Cross JA, Dawson WM, Thompson HF, Shanmugaratnam S, Savery NJ, Dodding MP, Hocker B, Woolfson DN Nat Chem Biol. 2022 Jul 14. pii: 10.1038/s41589-022-01076-6. doi:, 10.1038/s41589-022-01076-6. PMID:35836017^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.