%0 Journal Article
%T A photocaged orexin-B for spatiotemporally precise control of orexin signaling.
%A Duffet L
%A Tatarskiy PV
%A Harada M
%A Williams ET
%A Hartrampf N
%A Patriarchi T
%J Cell Chem Biol
%V 29
%N 12
%D 12 2022 15
%M 36481097
%F 9.039
%R 10.1016/j.chembiol.2022.11.007
%X Orexin neuropeptides carry out important neuromodulatory functions in the brain, yet tools to precisely control the activation of endogenous orexin signaling are lacking. Here, we developed a photocaged orexin-B (photo-OXB) through a C-terminal photocaging strategy. We show that photo-OXB is unable to activate its cognate receptors in the dark but releases functionally active native orexin-B upon uncaging by illumination with UV-visible (UV-vis) light (370-405 nm). We established an all-optical assay combining photo-OXB with a genetically encoded orexin biosensor and used it to characterize the efficiency and spatial profile of photo-OXB uncaging. Finally, we demonstrated that photo-OXB enables optical control over orexin signaling with fine temporal precision both in vitro and ex vivo. Thus, our photocaging strategy and photo-OXB advance the chemical biological toolkit by introducing a method for the optical control of peptide signaling and physiological function.