All-photonic kinase inhibitors: light-controlled release-and-report inhibition
Artikel i vetenskaplig tidskrift, 2024

Light-responsive molecular tools targeting kinases affords one the opportunity to study the underlying cellular function of selected kinases. In efforts to externally control lymphocyte-specific protein tyrosine kinase (LCK) activity, the development of release-and-report LCK inhibitors is described, in which (i) the release of the active kinase inhibitor can be controlled externally with light; and (ii) fluorescence is employed to report both the release and binding of the active kinase inhibitor. This introduces an unprecedented all-photonic method for users to both control and monitor real-time inhibitory activity. A functional cellular assay demonstrated light-mediated LCK inhibition in natural killer cells. The use of coumarin-derived caging groups resulted in rapid cellular uptake and non-specific intracellular localisation, while a BODIPY-derived caging group predominately localised in the cellular membrane. This concept of release-and-report inhibitors has the potential to be extended to other biorelevant targets where both spatiotemporal control in a cellular setting and a reporting mechanism would be beneficial.

Författare

Cassandra Fleming

Göteborgs universitet

Carlos Benitez-Martin

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Elin Bernson

Göteborgs universitet

Yongjin Xu

Göteborgs universitet

Linnea Kristenson

Göteborgs universitet

Tord Inghardt

AstraZeneca AB

Thomas Lundback

AstraZeneca AB

Fredrik B. Thoren

Göteborgs universitet

Morten Grötli

Göteborgs universitet

Joakim Andreasson

Chalmers, Kemi och kemiteknik, Kemi och biokemi

Chemical Science

2041-6520 (ISSN) 2041-6539 (eISSN)

Vol. 15 18 6897-6905

Ämneskategorier

Biokemi och molekylärbiologi

DOI

10.1039/d4sc00390j

Mer information

Senast uppdaterat

2024-10-03