Effects of stereochemistry, saturation, and hydrocarbon chain length on the ability of synthetic constrained azacyclic sphingolipids to trigger nutrient transporter down-regulation, vacuolation, and cell death.
Effects of stereochemistry, saturation, and hydrocarbon chain length on the ability of synthetic constrained azacyclic sphingolipids to trigger nutrient transporter down-regulation, vacuolation, and cell death.
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立体化学、饱和度和烃链长度对合成受限氮杂环鞘脂触发营养转运蛋白下调、空泡形成和细胞死亡能力的影响。
DOI：
10.1016/j.bmc.2016.07.038
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发表时间：
2016
影响因子：
3.5
通讯作者：
Hanessian,Stephen
中科院分区：
文献类型：
--
作者：
Perryman,MichaelS;Tessier,Jérémie;Wiher,Timothy;O'Donoghue,Heather;McCracken,AlisonN;Kim,SeongM;Nguyen,DeanG;Simitian,GrigorS;Viana,Matheus;Rafelski,Susanne;Edinger,AimeeL;Hanessian,Stephen
Constrained analogs containing a 2-hydroxymethylpyrrolidine core of the natural sphingolipids sphingosine, sphinganine,N,N-dimethylsphingosine andN-acetyl variants of sphingosine and sphinganine (C2-ceramide and dihydro-C2-ceramide) were synthesized and evaluated for their ability to down-regulate nutrient transporter proteins and trigger cytoplasmic vacuolation in mammalian cells. In cancer cells, the disruptions in intracellular trafficking produced by these sphingolipids lead to cancer cell death by starvation. Structure activity studies were conducted by varying the length of the hydrocarbon chain, the degree of unsaturation and the presence or absence of an aryl moiety on the appended chains, and stereochemistry at two stereogenic centers. In general, cytotoxicity was positively correlated with nutrient transporter down-regulation and vacuolation. This study was intended to identify structural and functional features in lead compounds that best contribute to potency, and to develop chemical biology tools that could be used to isolate the different protein targets responsible for nutrient transporter loss and cytoplasmic vacuolation. A molecule that produces maximal vacuolation and transporter loss is expected to have the maximal anti-cancer activity and would be a lead compound.
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酿酒酵母对新型免疫调节剂 FTY720 的遗传、生化和转录反应在很大程度上模仿了天然鞘脂植物鞘氨醇*
影响因子：
4.8
作者：
Carole A. Welsch;Lukas Roth;J. Goetschy;N. Movva
通讯作者：
N. Movva
DOI：
10.1016/s0021-9258(18)82288-8
发表时间：
1993-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Rick T. DobrowskySS;Craig Kamibayashili;Marc C. Mumbyli;Yusuf A. HannunSIJ
通讯作者：
Rick T. DobrowskySS;Craig Kamibayashili;Marc C. Mumbyli;Yusuf A. HannunSIJ
影响因子：
2.9
作者：
Schmouder, Robert;Serra, Denise;Bastien, Marie-Claude
通讯作者：
Bastien, Marie-Claude
影响因子：
6.6
作者：
Azuma, H;Takahara, S;Katsuoka, Y
通讯作者：
Katsuoka, Y
泛素通路蛋白影响酿酒酵母中新型免疫抑制药物 FTY720 的作用机制*
影响因子：
4.8
作者：
Carole A. Welsch;S. Hagiwara;Jean Francois Goetschy;N. Movva
通讯作者：
N. Movva