Short Photoswitchable Ceramides Enable Optical Control of Apoptosis
Johannes Morstein, Matthijs Kol, A. Novák, Suihan Feng, Shadi Khayyo, Konstantin Hinnah, Nasi Li-Purcell, Grace Pan, Benjamin M. Williams, Howard Riezman, G. Ekin Atilla‐Gokcumen, Joost C. M. Holthuis, Dirk Trauner
Abstract
We report short ceramide analogs that can be activated with light and further functionalized using azide–alkyne click chemistry. These molecules, termed scaCers, exhibit increased cell permeability compared to their long-chain analogs as demonstrated using mass spectrometry and imaging. Notably, scaCers enable optical control of apoptosis, which is not observed with long-chain variants. Additionally, they function as photoswitchable substrates for sphingomyelin synthase 2 (SMS2), exhibiting inverted light-dependence compared to their extended analogs.