Selective esterase-ester pair for targeting small molecules with cellular specificity
Selective esterase-ester pair for targeting small molecules with cellular specificity
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DOI：
10.1073/pnas.1111943109
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发表时间：
2012-03-27
影响因子：
11.1
通讯作者：
Lavis, Luke D.
中科院分区：
文献类型：
--
作者：
Tian, Lin;Yang, Yunlei;Lavis, Luke D.
小分子是测量和调节细胞内信号通路的重要工具。在复杂组织中使用化合物的长期限制是无法将生物活性小分子靶向特定的细胞类别。在这里，我们描述了一个通用的酯酶-酯对能够有针对性地提供小分子的活细胞和组织的细胞特异性。我们使用荧光分子来快速识别一个小的酯掩蔽基序，该基序对内源性酯酶是稳定的，但被外源性酯酶有效地去除。这种策略允许在复杂的生物环境中轻松靶向染料和药物，以标记特定的细胞类型，照亮间隙连接连接，并干扰不同的细胞亚群。我们期望这种方法具有将许多小分子特异性递送至限定的细胞群体的通用性。
Small molecules are important tools to measure and modulate intracellular signaling pathways. A longstanding limitation for using chemical compounds in complex tissues has been the inability to target bioactive small molecules to a specific cell class. Here, we describe a generalizable esterase-ester pair capable of targeted delivery of small molecules to living cells and tissue with cellular specificity. We used fluorogenic molecules to rapidly identify a small ester masking motif that is stable to endogenous esterases, but is efficiently removed by an exogenous esterase. This strategy allows facile targeting of dyes and drugs in complex biological environments to label specific cell types, illuminate gap junction connectivity, and pharmacologically perturb distinct subsets of cells. We expect this approach to have general utility for the specific delivery of many small molecules to defined cellular populations.