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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reactive polymer enables efficient in vivo bioorthogonal chemistry
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Reactive polymer enables efficient in vivo bioorthogonal chemistry

机译：反应性聚合物可实现有效的体内生物正交化学

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摘要

There has been intense interest in the development of selective bioorthogonal reactions or "click" chemistry that can proceed in live animals. Until now however, most reactions still require vast surpluses of reactants because of steep temporal and spatial concentration gradients. Using computational modeling and design of pharmacokinetically optimized reactants, we have developed a predictable method for efficient in vivo click reactions. Specifically, we show that polymer modified tetrazines (PMT) are a key enabler for in vivo bioorthogonal chemistry based on the very fast and catalyst-free [4 + 2] tetrazine/trans-cyclooctene cycloaddition. Using fluorescent PMT for cellular resolution and ~(18)F labeled PMT for whole animal imaging, we show that cancer cell epitopes can be easily reacted in vivo. This generic strategy should help guide the design of future chemistries and find widespread use for different in vivo bioorthogonal applications, particularly in the biome-dical sciences.
机译：人们对开发可以在活体动物中进行的选择性生物正交反应或“点击”化学产生了浓厚的兴趣。然而，到目前为止，由于陡峭的时间和空间浓度梯度，大多数反应仍需要大量的反应物。使用计算模型和药代动力学优化的反应物设计，我们已经开发出一种有效的体内点击反应的可预测方法。具体来说，我们显示基于非常快速且无催化剂的[4 + 2]四嗪/反式环辛烯环加成反应，聚合物改性的四嗪（PMT）是体内生物正交化学的关键推动力。使用荧光PMT用于细胞分辨率和〜（18）F标记的PMT用于整个动物成像，我们显示癌细胞表位可以在体内轻易反应。这种通用策略应有助于指导未来化学的设计，并在不同的体内生物正交应用中获得广泛应用，尤其是在生物医学领域。

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  • 作者

    Neal K. Devaraj; Greg M. Thurber; Edmund J. Keliher; Brett Marinelli; Ralph Weissleder;

  • 作者单位

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston,MA 02114;

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston,MA 02114;

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston,MA 02114;

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston,MA 02114;

    Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Simches Research Building, 185 Cambridge Street, Boston,MA 02114;

  • 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

    in vivo chemistry; pharmacokinetics; PET imaging; intravital microscopy; pretargeting;

    机译：体内化学;药代动力学PET成像;活体显微镜检查预定位;

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