In this section
@article{McCann:2026:10.1039/D6SC06137K,
author = {McCann, S and Prischich, D and Scobel, K and Worm, D and Thawani, A and Mori, M and Tan, YS and Barnard, A and Fuchter, M},
doi = {10.1039/D6SC06137K},
journal = {Chemical Science},
title = {Long-lived azobispyrazole stapled peptides for light-activated inhibition of protein-protein interactions},
url = {http://dx.doi.org/10.1039/D6SC06137K},
year = {2026}
}
TY - JOUR
AB - Photoswitches can be used to optically control the bioactive conformation of molecules through E-Z photoisomerisation, thereby enabling precise regulation of biological interactions with light. Herein, we describe the first use of a photoswitchable azobispyrazole cross-linker to generate light-responsive (i, i+7)-stapled Bak7287 and p5317-28 peptides. Photoisomerisation (E→Z) of the stapled peptides enhanced helical content and led to an increase in binding affinity for target proteins Bcl-xL and MDM2, an effect that was reversible upon back-irradiation to the Z isomer. The novel azobispyrazole cross-linker demonstrated excellent photochemical properties including near-quantitative photoisomerisation and long thermal half-life of 65 days at 21°C. These properties were retained in the stapled peptide form of AzBisPy-Bak72-87 (0.5-year half-life) and were tolerant to biological assay conditions. Our work expands the repertoire of photoswitches designed for peptide stapling and demonstrates the ability of azobispyrazolestapled peptides to modulate protein-protein interactions in a system where binding is controlled exclusively by light, independent of thermal relaxation, over a timescale of several weeks.
AU - McCann,S
AU - Prischich,D
AU - Scobel,K
AU - Worm,D
AU - Thawani,A
AU - Mori,M
AU - Tan,YS
AU - Barnard,A
AU - Fuchter,M
DO - 10.1039/D6SC06137K
PY - 2026///
SN - 2041-6520
TI - Long-lived azobispyrazole stapled peptides for light-activated inhibition of protein-protein interactions
T2 - Chemical Science
UR - http://dx.doi.org/10.1039/D6SC06137K
UR - https://pubs.rsc.org/sc/article/doi/10.1039/D6SC06137K/1376016/Long-Lived-Azobispyrazole-Stapled-Peptides-for
ER -
Dr Anna Barnard
Wellcome Trust Sir Henry Dale Fellow
Department of Chemistry
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a.barnard@imperial.ac.uk
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