Selenomethionine as an expressible handle for bioconjugations.
Selenomethionine as an expressible handle for bioconjugations.
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硒代蛋氨酸作为生物共轭的可表达手柄。
DOI：
10.1073/pnas.2005164118
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发表时间：
2021
影响因子：
11.1
通讯作者：
Dawson,PhilipE
中科院分区：
文献类型：
--
作者：
Flood,DillonT;Hintzen,JordiCJ;Knouse,KyleW;Hill,DavidE;Lu,Chenxi;Cistrone,PhilipA;Chen,JasonS;Otomo,Takanori;Dawson,PhilipE
定点选择性的化学生物偶联反应是化学生物学家的有利工具。在对硒蛋氨酸(SEM)苄基化反应的仔细研究的指导下，我们对反应进行了改进，以满足实际蛋白质生物偶联的要求。扫描电子显微镜很容易通过营养缺陷型表达引入，并表现出独特的亲核性质，即使在半胱氨酸存在的情况下也可以选择性地对其进行修饰。由此得到的苯基硒加合物在生理pH下是稳定的，对谷胱甘肽选择性不稳定，并体现了广泛可调的裂解谱。具体地说，4-溴甲基苯乙酰(BrMePAA)连接物已被应用于复杂有机分子与含扫描电子显微镜的蛋白质的有效偶联。这种生物偶联工具箱的扩展在开发化学增强蛋白质方面具有广阔的潜力。
Site-selective chemical bioconjugation reactions are enabling tools for the chemical biologist. Guided by a careful study of the selenomethionine (SeM) benzylation, we have refined the reaction to meet the requirements of practical protein bioconjugation. SeM is readily introduced through auxotrophic expression and exhibits unique nucleophilic properties that allow it to be selectively modified even in the presence of cysteine. The resulting benzylselenonium adduct is stable at physiological pH, is selectively labile to glutathione, and embodies a broadly tunable cleavage profile. Specifically, a 4-bromomethylphenylacetyl (BrMePAA) linker has been applied for efficient conjugation of complex organic molecules to SeM-containing proteins. This expansion of the bioconjugation toolkit has broad potential in the development of chemically enhanced proteins.