title: Synthesis and photochemical properties of PEGylated coumarin-caged ceramides for cell studies.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, NY 11367, USA. Electronic address: Youngah.Kim@qc.cuny.edu.
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Kim
authors.affiliation: National Research Council of Canada, Ottawa, ON K1A 0R6, Canada; Department of Chemistry, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
authors.forename: Jenna
authors.initials: J
authors.lastname: Day
authors.affiliation: National Research Council of Canada, Ottawa, ON K1A 0R6, Canada; Department of Chemistry, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Lirette
authors.affiliation: National Research Council of Canada, Ottawa, ON K1A 0R6, Canada.
authors.forename: Willard J
authors.initials: WJ
authors.lastname: Costain
authors.affiliation: National Research Council of Canada, Ottawa, ON K1A 0R6, Canada.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Johnston
authors.affiliation: Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, NY 11367, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
mesh_terms: D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects*; D003374:Coumarins / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D010782:Photolysis / Q000528:radiation effects*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
chemical_list: D002518:Ceramides; D003374:Coumarins; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols; D020169:Caspases
keywords: Ceramide; PEGylated coumarin cages; Photocage; Photolysis