Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

De novo designed peptides for cellular delivery and subcellular localisation

Rhys, Guto G., Cross, Jessica A., Dawson, William M., Thompson, Harry F., Shanmugaratnam, Sooruban, Savery, Nigel J., Dodding, Mark P., Höcker, Birte and Woolfson, Derek N. 2022. De novo designed peptides for cellular delivery and subcellular localisation. Nature Chemical Biology 18 (9) , pp. 999-1004. 10.1038/s41589-022-01076-6

[thumbnail of PP.pdf]
Preview
PDF - Accepted Post-Print Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Publisher: Nature Research
ISSN: 1552-4450
Date of First Compliant Deposit: 1 December 2022
Date of Acceptance: 3 June 2022
Last Modified: 07 Nov 2023 02:46
URI: https://orca.cardiff.ac.uk/id/eprint/153756

Citation Data

Cited 13 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics