Synthesis and Cellular Labeling of Multifunctional Phosphatidylinositol Bis- and Trisphosphate Derivatives.
Synthesis and Cellular Labeling of Multifunctional Phosphatidylinositol Bis- and Trisphosphate Derivatives.
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多功能磷脂酰肌醇二磷酸和三磷酸衍生物的合成和细胞标记。
DOI：
10.1002/anie.202103599
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发表时间：
2021-09-01
期刊：
影响因子：
--
通讯作者：
Schultz C
中科院分区：
文献类型：
--
作者：
Müller R;Kojic A;Citir M;Schultz C
我们合成了第一种多官能化的磷酸肌醇多磷酸衍生物，其特征在于可光移除的保护基团（“笼”）、可光交联的二氮杂环丙烯基团和可用于点击化学的末端炔基。我们证明，脂质衍生物容易进入细胞。在通过点击化学进行光交联、细胞固定和荧光标记之后，我们确定了脂质释放之前和之后脂质衍生物的细胞内位置。我们发现，有PI（3，4）P2和PI（3，4，5）P3衍生物的质膜，打开有趣的可能性，有这些脂质的主动运输参与。我们采用光交联和点击化学功能来分析PI（3，4，5）P3结合蛋白的蛋白质组。从后者出发，我们通过RNAi证实了推测的脂质结合蛋白ATP 11A和MPP 6参与PI（3，4，5）P3向质膜的转运。合成了第一种多官能化的磷酸肌醇多磷酸衍生物，其特征在于可光去除的保护基团、可光交联的二氮杂环丙烯基团和可用于点击化学的末端炔基。脂质衍生物很容易进入细胞，并观察到未包裹的衍生物快速运输到质膜，这开启了这些脂质参与主动运输的有趣可能性。
We synthesized the first multifunctionalized phosphoinositide polyphosphate derivatives featuring a photo‐removable protecting group (“cage”), a photo‐crosslinkable diazirine group, and a terminal alkyne group useful for click chemistry. We demonstrate that the lipid derivatives readily enter cells. After photo‐crosslinking, cell fixation and fluorescent tagging via click chemistry, we determined the intracellular location of the lipid derivatives before and after uncaging of the lipids. We find that there is rapid trafficking of PI(3,4)P2 and PI(3,4,5)P3 derivatives to the plasma membrane, opening the intriguing possibility that there is active transport of these lipids involved. We employed the photo‐crosslinking and click chemistry functions to analyze the proteome of PI(3,4,5)P3‐binding proteins. From the latter, we validated by RNAi that the putative lipid binding proteins ATP11A and MPP6 are involved in the transport of PI(3,4,5)P3 to the plasma membrane. The first multifunctionalized phosphoinositide polyphosphate derivatives featuring a photo‐removable protecting group, a photo‐crosslinkable diazirine group, and a terminal alkyne group useful for click chemistry were synthesized. The lipid derivatives readily enter cells and rapid trafficking of uncaged derivatives to the plasma membrane is observed, opening the intriguing possibility that there is active transport of these lipids involved.
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影响因子：
16
作者：
Park, Wei Sun;Do Heo, Won;Teruel, Mary N.
通讯作者：
Teruel, Mary N.
DOI：
10.1073/pnas.1611096114
发表时间：
2017-02-14
影响因子：
11.1
作者：
Hoeglinger, Doris;Nadler, Andre;Schultz, Carsten
通讯作者：
Schultz, Carsten
DOI：
10.1126/science.aab1370
发表时间：
2015-07-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chung J;Torta F;Masai K;Lucast L;Czapla H;Tanner LB;Narayanaswamy P;Wenk MR;Nakatsu F;De Camilli P
通讯作者：
De Camilli P
影响因子：
64.8
作者：
Posor, York;Eichhorn-Gruenig, Marielle;Haucke, Volker
通讯作者：
Haucke, Volker
影响因子：
64.5
作者：
Niphakis MJ;Lum KM;Cognetta AB 3rd;Correia BE;Ichu TA;Olucha J;Brown SJ;Kundu S;Piscitelli F;Rosen H;Cravatt BF
通讯作者：
Cravatt BF