Transition Metal-Free Tryptophan-Selective Bioconjugation of Proteins
Transition Metal-Free Tryptophan-Selective Bioconjugation of Proteins
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DOI：
10.1021/jacs.6b06692
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发表时间：
2016-08-31
影响因子：
15
通讯作者：
Kanai, Motomu
中科院分区：
文献类型：
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作者：
Seki, Yohei;Ishiyama, Takashi;Kanai, Motomu
天然蛋白质的化学修饰可以促进超自然蛋白质的产生：这些功能不容易通过依赖于遗传操作的互补方法获得。然而，实现对选择性的精确控制，同时保持结构：完整性和同质性仍然是一个严峻的挑战。在此，我们报告了一种无过渡金属的方法，用于蛋白质的选择性生物缀合，该方法基于有机基团并在环境条件下操作。该方法表现出低水平的交叉反应性，并使蛋白质的高级结构和其中的各种官能团不受影响：靶向丰度较低的氨基酸的策略有助于形成结构均匀的缀合物，其甚至可能适用于蛋白质。结晶学不存在有毒金属和生物化学不相容的条件允许天然蛋白质如抗体和致病性聚集蛋白质的快速功能调节，并且该方法因此可以容易地找到治疗应用。
Chemical modifications' of native proteins can facilitate production of supernatural protein :functions that are not easily accessible by complementary methods relying on genetic manipulations. However, accomplishing precise control over selectivity while maintaining structural:. integrity and homogeneity still represents a fOrmidable, challenge. Herein, we report a transition metal-free method for tryptophan-selective bioconjugation of proteins that is based on an organoradical and operates under ambient conditions. This method exhibits low levels of cross-reactivity and leaves.higher-order structures of the protein and various functional groups therein unaffected: The strategy to,target less abundant amino acids contributes to the formation of structurally homogeneous conjugates, which may even be suitable for protein. crystallography. The absence of toxic metals and biochemi-i cally incompatible conditions allows a rapid functional- modulation of native proteins such as antibodies and pathogenic aggregative proteins, and this method may thus easily find therapeutic applications.