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Controlling Protein Functionalities With Temporal and Cellular/Subcellular Dimensions of Spatial Resolution With Molecular Photoswitches
Author(s) -
Sahu Saugata,
Amrutha Ammathnadu S.,
Tamaoki Nobuyuki
Publication year - 2025
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.22106
Subject(s) - photoswitch , chemistry , biophysics , ligand (biochemistry) , nanotechnology , computational biology , receptor , biology , biochemistry , materials science , photochemistry
ABSTRACT The use of photoswitchable ligand to control the protein functionalities and related downstream effects in an on‐off manner is an active research area in photopharmacology and medicinal chemistry. Temporal control grants a privilege to identify the crucial role of a particular receptor in biological occurrences without destroying the protein permanently. Additionally, light can be applied site‐selectively to regulate protein functionality with cellular and sub‐cellular levels of spatial resolutions. The spatiotemporal resolution enables the probing of a specific receptor, a receptor isoform, or a particular signalling pathway. This reversible and fast spatiotemporal control is highly beneficial in studying protein functionalities in highly dynamic biological processes, including but not limited to signal transduction, neurotransmission, cell divisions, immune response, protein folding, and protein degradation. Though several light‐active ligands have been developed to control protein functionality in an on‐off manner efficiently, only a few reports on protein functionality with spatial resolution exist in the literature. Major challenges to achieve efficient photoswitches to study protein functionalities are efficient synthesis strategy, photostability of the ligand, bidirectional visible light switching ability and most importantly precise controlling of the local concentration of desired photoisomer using light. The site‐specific localization of the active photoisomer depends on multiple factors like the nature of the photoswitch, the binding affinity of both photoisomers, molecular diffusion and light irradiation conditions. The present review discusses suitable techniques and the role of different factors in achieving cellular and subcellular dimension control in protein functionality. Multiple strategies are discussed, along with their advantages and limitations, to explore the enormous potentiality of these approaches in manipulating protein functionality.