Development and Optimization of Glaser-Hay Bioconjugations
Development and Optimization of Glaser-Hay Bioconjugations
复制标题
DOI：
10.1002/anie.201502676
复制
发表时间：
2015-08-03
影响因子：
16.6
通讯作者：
Young, Douglas D.
中科院分区：
文献类型：
--
作者：
Lampkowski, Jessica S.;Villa, Jordan K.;Young, Douglas D.
生物共轭物在生物医学中的流行需要开发新的机制来促进其制备。为此，我们检查了 Glaser-Hay 偶联在水性环境中的翻译，并证明了其作为生物正交缀合反应的潜力。这种优化的、新颖的水性 Glaser-Hay 反应可用于利用用炔基非天然氨基酸表达的蛋白质来开发生物缀合物。非天然氨基酸技术提供了其他方法无法实现的一定程度的生物正交性和特异性。此外，反应的范围通过蛋白质-小分子偶联、小分子-固体支持物偶联和蛋白质-固体支持物固定来证明。
The prevalence of bioconjugates in the biomedical sciences necessitates the development of novel mechanisms to facilitate their preparation. Towards this end, the translation of the Glaser-Hay coupling to an aqueous environment is examined, and its potential as a bioorthogonal conjugation reaction is demonstrated. This optimized, novel, and aqueous Glaser-Hay reaction is applied towards the development of bioconjugates utilizing protein expressed with an alkynyl unnatural amino acid. Unnatural amino acid technology provides a degree of bioorthognality and specificity not feasible with other methods. Moreover, the scope of the reaction is demonstrated through protein-small molecule couplings, small-molecule-solid-support couplings, and protein-solid-support immobilizations.