125I-Tetrazines and Inverse-Electron-Demand Diels-Alder Chemistry: A Convenient Radioiodination Strategy for Biomolecule Labeling, Screening, and Biodistribution Studies
125I-Tetrazines and Inverse-Electron-Demand Diels-Alder Chemistry: A Convenient Radioiodination Strategy for Biomolecule Labeling, Screening, and Biodistribution Studies
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DOI：
10.1021/acs.bioconjchem.5b00609
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发表时间：
2016-01-01
影响因子：
4.7
通讯作者：
Valliant, John F.
中科院分区：
文献类型：
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作者：
Albu, Silvia A.;Al-Karmi, Salma A.;Valliant, John F.
开发了一种制备放射性碘标记四嗪的简便方法，使得生物正交逆电子需求Diels-Alder反应可用于用碘-125标记生物分子用于体外筛选和体内生物分布研究。四嗪通过采用高产率的氧化性卤代脱锡烷基化反应来制备，该反应伴随氧化二氢四嗪前体。该产品与反式环辛烯衍生物反应迅速有效。通过抗体和激素标记实验以及使用标准分析方法、体外测定和定量生物分布研究（后者与Bolton-Hunter和直接碘化方法进行直接比较）评价产品证明了实用性。所描述的方法提供了常规蛋白质碘化方法的方便和有利的替代方法，可以加速生物治疗药物的临床前开发和评估。
A convenient method to prepare radioiodinated tetrazines was developed, such that a bioorthogonal inverse electron demand Diels-Alder reaction can be used to label biomolecules with iodine-125 for in vitro screening and in vivo biodistribution studies. The tetrazine was prepared by employing a high-yielding oxidative halo destannylation reaction that concomitantly oxidized the dihydrotetrazine precursor. The product reacts quickly and efficiently with trans-cyclooctene derivatives. Utility was demonstrated through antibody and hormone labeling experiments and by evaluating products using standard analytical methods, in vitro assays, and quantitative biodistribution studies where the latter was performed in direct comparison to Bolton-Hunter and direct iodination methods. The approach described provides a convenient and advantageous alternative to conventional protein iodination methods that can expedite preclinical development and evaluation of biotherapeutics.