In this section
@article{Worm:2023,
author = {Worm, D and Grabe, G and Vieira, de Castro G and Rabinovich, S and Warm, I and Isherwood, K and Helaine, S and Barnard, A},
journal = {ACS Chemical Biology},
pages = {2485--2494},
title = {Stapled Phd peptides inhibit Doc toxin induced growth arrest in Salmonella},
url = {https://pubs.acs.org/doi/10.1021/acschembio.3c00411},
volume = {18},
year = {2023}
}
TY - JOUR
AB - Bacterial toxin inhibition is a promising approach for overcoming antibiotic failure. In Salmonella, knock-out of the toxin Doc has been shown to significantly reduce the formation of antibiotic-tolerant persisters. Doc is a kinase that is inhibited in non-tolerant cells by its cognate antitoxin, Phd. In this work, we have developed first-in-class stapled peptide antitoxin mimetics based on the Doc inhibitory sequence of Phd. After making a series of substitutionsto improve bacterial uptake, we have identified a lead stapled Phd peptide able to counteract Doc toxicity in Salmonella. This provides an exciting starting point for the further development of therapeutic peptides capable of reducing antibiotic persistence in pathogenic bacteria.
AU - Worm,D
AU - Grabe,G
AU - Vieira,de Castro G
AU - Rabinovich,S
AU - Warm,I
AU - Isherwood,K
AU - Helaine,S
AU - Barnard,A
EP - 2494
PY - 2023///
SN - 1554-8929
SP - 2485
TI - Stapled Phd peptides inhibit Doc toxin induced growth arrest in Salmonella
T2 - ACS Chemical Biology
UR - https://pubs.acs.org/doi/10.1021/acschembio.3c00411
UR - http://hdl.handle.net/10044/1/107471
VL - 18
ER -
Dr Anna Barnard
Wellcome Trust Sir Henry Dale Fellow
Department of Chemistry
Imperial College London
Wood Lane
London W12 0BZ
a.barnard@imperial.ac.uk
Tel: +44 (0)20 7594 8551