Reactive polymer enables efficient in vivo bioorthogonal chemistry
Reactive polymer enables efficient in vivo bioorthogonal chemistry
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DOI：
10.1073/pnas.1113466109
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发表时间：
2012-03-27
影响因子：
11.1
通讯作者：
Weissleder, Ralph
中科院分区：
文献类型：
--
作者：
Devaraj, Neal K.;Thurber, Greg M.;Weissleder, Ralph
人们对可以在活体动物中进行的选择性生物正交反应或“点击”化学的发展产生了浓厚的兴趣。然而，到目前为止，大多数反应仍然需要大量的反应物盈余，因为时间和空间浓度梯度很大。利用计算模型和药代动力学优化反应物的设计，我们开发了一种可预测的有效体内点击反应的方法。具体地说，我们发现聚合物改性四嗪(PMT)是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的体内生物正交化学的关键促进剂。使用荧光PMT进行细胞分辨和F-18标记PMT进行整体动物成像，我们发现癌细胞表位在体内可以很容易地反应。这种通用策略应该有助于指导未来的化学设计，并发现不同的体内生物正交应用的广泛用途，特别是在生物医学科学中。
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 F-18 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 biomedical sciences.