Design Principles for Cationic, Astrocyte-Targeted Probes.
Design Principles for Cationic, Astrocyte-Targeted Probes.
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阳离子星形胶质细胞靶向探针的设计原则。
DOI：
10.1002/cbic.201800692
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Laughlin,ScottT
中科院分区：
文献类型：
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作者：
Preston,AlyssaN;Farr,JoshuaD;Tan,KevinC;Cervasio,DanielleA;Butkus,LaurenR;Laughlin,ScottT
脑的星形胶质细胞在正常和病理性脑过程中起关键作用。在大脑中存在许多其他细胞类型的情况下，将小分子靶向星形胶质细胞将为其可视化和操作提供有用的工具。在此，我们探索了最近描述的星形胶质细胞标记物的合成修饰的功能后果，该标记物由明亮的基于罗丹明的荧光团和星形胶质细胞靶向部分组成。我们改变了性质的靶向部分，以探测星形胶质细胞的疏水性，电荷和pKa的依赖性，当暴露于星形胶质细胞和神经元分离的小鼠皮层。我们发现，+2的总分子电荷和具有杂环芳香胺的靶向部分是特异性和稳健的星形胶质细胞标记的重要要求。这些结果为设计具有独特特性的星形胶质细胞靶向分子工具提供了基础，包括代谢物传感或光遗传学控制。
The brain's astrocytes play key roles in normal and pathological brain processes. Targeting small molecules to astrocytes in the presence of the many other cell types in the brain will provide useful tools for their visualization and manipulation. Herein, we explore the functional consequences of synthetic modifications to a recently described astrocyte marker composed of a bright rhodamine‐based fluorophore and an astrocyte‐targeting moiety. We altered the nature of the targeting moiety to probe the dependence of astrocyte targeting on hydrophobicity, charge, and pKawhen exposed to astrocytes and neurons isolated from the mouse cortex. We found that an overall molecular charge of +2 and a targeting moiety with a heterocyclic aromatic amine are important requirements for specific and robust astrocyte labeling. These results provide a basis for engineering astrocyte‐targeted molecular tools with unique properties, including metabolite sensing or optogenetic control.