Abstract

CANCELLED - Biophotonic Nanoswitches to Control Cell Fate

Rudolf Allemann, Distinguished Research Professor, Cardiff University

Dynamic interactions between proteins underpin all key cellular processes. Despite their importance, intracellular protein-protein interactions have proven inherently difficult to target because protein interfaces are often extensive, shallow and mainly hydrophobic with only limited opportunities for selective chemical intervention with small molecules. We report the synthesis of light-responsive short peptides based on alpha-helices derived from Bcl-2 proteins and show that the combination of azobenzene isomerisation by external light pulsing and subsequent rapid thermal reversion gives such conjugated peptides switch-like properties to trigger the intrinsic apoptotic pathway in human cancer cells. Biophotonic nanoswitches have key advantages over small molecule agents for modulating protein-protein controlled cellular pathways. They exploit native sequences replicating the target selectivity of the parent protein. The controlled delivery of a pulse of ‘activated’ peptide both matches the temporal scale for protein interactions and provides an in situ perturbation that is discrete, predictable, programmable and not subject to a ‘wash-out’ procedure. Finally, photonic switching is non-invasive and can be developed to encompass novel spectral characteristics and patterning by selective spatial activation of bulk peptide delivery. Biophotonic nanoswitches offer opportunities for the development of medicines and as research tools for the study of fundamental mechanisms in cell biology.