Accelerated Protein Synthesis via One-Pot Ligation-Deselenization Chemistry
Accelerated Protein Synthesis via One-Pot Ligation-Deselenization Chemistry
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DOI：
10.1016/j.chempr.2017.04.003
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发表时间：
2017-05-11
期刊：
影响因子：
23.5
通讯作者：
Payne, Richard J.
中科院分区：
文献类型：
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作者：
Mitchell, Nicholas J.;Sayers, Jessica;Payne, Richard J.
肽连接化学通过促进合成蛋白质的获得而彻底改变了蛋白质科学。在这里，我们描述了在β-硒代天冬氨酸和γ-硒代谷氨酸的无添加剂连接-脱硒化学的发展，其使得能够在前所未有的时间尺度上产生天然多肽产物。脱硒步骤在未保护的硒代半胱氨酸存在下具有化学选择性，这在硒蛋白K的合成中突出显示。该方法的威力也通过三种蜱源性凝血酶抑制蛋白的合成来展示，每种蛋白都在几个小时内组装、纯化和分离用于生物测定。这里描述的方法应该作为一个强大的手段，获得合成蛋白质，包括治疗铅，在未来。
Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at beta-selenoaspartate and gamma-selenoglutamate that enables the generation of native polypeptide products on unprecedented timescales. The deselenization step is chemoselective in the presence of unprotected selenocysteine, which is highlighted in the synthesis of selenoprotein K. The power of the methodology is also showcased through the synthesis of three tick-derived thrombin-inhibiting proteins, each of which were assembled, purified, and isolated for biological assays within a few hours. The methodology described here should serve as a powerful means of accessing synthetic proteins, including therapeutic leads, in the future.