Synthesis and photochemical properties of PEGylated coumarin-caged ceramides for cell studies

• Photocleavable ceramides with long- and very-long N-acyl chain were synthesized by introducing a short PEGylated coumarin cage.
• Caged ceramides showed efficient photo-uncaging with long-wavelength UV light (350 nm).
• Preliminary studies demonstrated uptake of caged ceramides by cells and photo-induced changes in cell viability.

Caged ceramide analogues (C6-, C16-, C18-, C22- and C24-Cer) have been prepared by introducing a hydrophilic coumarin-based cage bearing a short polyethylene glycol (PEG) chain. (6-Bromo-7-mTEGylated-coumarin-4-yl)methyl (Btc) caged ceramide showed efficient photo-uncaging to release the parent ceramide upon direct exposure to 350 nm UV light; in contrast (7-mTEGylated-coumarin-4-yl)methyl (Tc) caged ceramide was photolysed more slowly. In preliminary experiments, Btc-caged ceramides were taken up by cells and their photolysis led to decreases in cell viability, but not to activation of caspase enzymes, suggesting that either reactive oxygen species or an alternate caspase-independent pathway may be responsible for the decreases in cell viability caused by photolysis of caged ceramides.

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