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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Selective esterase-ester pair for targeting small molecules with cellular specificity
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Selective esterase-ester pair for targeting small molecules with cellular specificity

机译：选择性酯酶-酯对，用于靶向具有细胞特异性的小分子

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摘要

Small molecules are important tools to measure and modulate in-tracellular 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 fkiorogenic 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.
机译：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，我们描述了一种通用化的酯酶-酯对，能够将小分子靶向递送至具有细胞特异性的活细胞和组织。我们使用致生分子来快速识别对内源酯酶稳定但被外源酯酶有效去除的小的酯掩蔽基序。这种策略允许在复杂的生物环境中轻松地靶向染料和药物，以标记特定的细胞类型，阐明缺口连接的连通性，并在药理上扰动不同的细胞亚群。我们期望这种方法对于将许多小分子特异性递送至确定的细胞群具有普遍的实用性。

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  • 作者

    Lin Tian; Yunlei Yang; Laura M. Wysocki; Alma C. Arnold; Amy Hu; Balaji Ravichandran; Scott M. Sternson; Loren L. Looger; Luke D. Lavis;

  • 作者单位

    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147;

    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147;

    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147;

    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147;

    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147;

    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147;

    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147;

    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147;

    Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cellular imaging; microscopy; enzyme substrates; fluorophores; pharmacological agents;

    机译：细胞成像显微镜酶底物;荧光团;药理剂;

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