Short Photoswitchable Ceramides Enable Optical Control of Apoptosis

Abstract

We report short ceramide analogs that can be activated with light and further functionalized using azide-alkyne click chemistry. These molecules, termed <b>scaCers</b>, exhibit increased cell permeability compared to their long-chain analogs as demonstrated using mass spectrometry and imaging. Notably, <b>scaCers</b> 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.