基于生物兼容的硒醇转换反应发展硒蛋白的研究工具

自从硒半胱氨酸（Sec）被发现是构成蛋白质的第21种氨基酸以来，目前已经在人体内鉴定出25种硒蛋白（含有Sec残基的蛋白）。但是，由于研究工具的缺乏，除了几类常见的硒蛋白外，近半数硒蛋白的功能还不清楚。在此我们基于Sec的特殊结构（可以转化为脱氢丙氨酸（DHA），一个具有迈克尔受体结构的亲电分子）和硒元素的特殊化学性质（硒醇的高亲核性和硒醚的氧化-消除反应），发展生物兼容的化学反应，将硒蛋白中的Sec残基转化为DHA残基。在此基础上，利用DHA的亲电性，发展多类DHA的衍生试剂，最终实现对复杂生物样品中硒蛋白的高效和精准衍生，建立研究硒蛋白的新方法。由于此方法的核心是硒醇的转换，因而我们将其命名为“硒醇转换”法。进一步，我们将基于新发展的“硒醇转换”法，开展硒蛋白的研究工作，以揭示硒蛋白的未知功能。

An increasing number of selenoproteins have been discovered since the selenocysteine (Sec) was identified as the 21st amino acid for protein synthesis. To date, twenty-five selenoproteins have been identified in human proteomes. However, nearly half of selenoproteins’ functions are not clear due to the lack of tools. Based on the unique structure of Sec and the chemical properties of selenium, we will develop a series of biocompatible reactions for selective and efficient derivatization of selenoproteins, which we term as a “selenol switch” protocol. In this protocol, The Sec residue in selenoproteins is selectively converted to a dehydroalanine (DHA) residue, which is then labeled with a nucleophile decorated with diverse tags. With this protocol, we may achieve specific enrichment, label and detection of selenoproteins from human proteomes. Furthermore, we will apply the selenol switch protocol to study selenoproteins, and expect to disclose novel functions of selenoproteins.