用于细胞研究的聚乙二醇化香豆素笼蔽神经酰胺的合成及光化学性质
Synthesis and photochemical properties of PEGylated coumarin-caged ceramides for cell studies.
作者信息
Kim Young Ah, Day Jenna, Lirette Carol Ann, Costain Willard J, Johnston Linda J, Bittman Robert
机构信息
Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, NY 11367, USA.
National Research Council of Canada, Ottawa, ON K1A 0R6, Canada; Department of Chemistry, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
出版信息
Chem Phys Lipids. 2016 Jan;194:117-24. doi: 10.1016/j.chemphyslip.2015.07.006. Epub 2015 Jul 19.
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.
通过引入带有短聚乙二醇（PEG）链的亲水性香豆素基笼状结构，制备了笼状神经酰胺类似物（C6-、C16-、C18-、C22-和C24-神经酰胺）。（6-溴-7-甲氧基三乙二醇化香豆素-4-基）甲基（Btc）笼状神经酰胺在直接暴露于350 nm紫外光时表现出高效的光解笼效应，释放出母体神经酰胺；相比之下，（7-甲氧基三乙二醇化香豆素-4-基）甲基（Tc）笼状神经酰胺的光解速度较慢。在初步实验中，Btc笼状神经酰胺被细胞摄取，其光解导致细胞活力下降，但未激活半胱天冬酶，这表明活性氧或另一种不依赖半胱天冬酶的途径可能是笼状神经酰胺光解导致细胞活力下降的原因。
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