Traceless native chemical ligation of lipid-modified peptide surfactants by mixed micelle formation
Traceless native chemical ligation of lipid-modified peptide surfactants by mixed micelle formation
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DOI：
10.1038/s41467-020-16595-w
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发表时间：
2020-06-03
影响因子：
16.6
通讯作者：
Devaraj, Neal K.
中科院分区：
文献类型：
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作者：
Jin, Shuaijiang;Brea, Roberto J.;Devaraj, Neal K.
生物学利用多种策略，包括在脂质囊泡中的隔离，通过增加反应物的有效摩尔浓度来提高化学反应的速率和特异性。我们发现胶束辅助反应可以促进肽-硫酯（其中硫酯离去基含有类脂烷基链）和被类脂部分修饰的半胱氨酸肽之间的天然化学连接（ncl）。每个肽段的疏水脂质修饰促进混合胶束的形成，使反应肽靠近，提高反应速率。该方法可以使用低浓度的反应物快速合成多肽，而不需要硫醇催化剂。在NCL后，脂质部分被去除以产生未经修饰的结扎产物。这种基于胶束的方法有助于生成天然肽，如magainin2，以及蛋白质泛素的衍生化。由脂质修饰的反应物形成的混合胶束显示出以无痕方式加速化学反应的希望。在脂质囊泡中封存反应物是生物系统中普遍采用的一种提高化学反应速率和特异性的策略。在这里，作者表明胶束辅助反应促进了肽硫酯和脂类修饰的半胱氨酸肽之间的天然化学连接。
Biology utilizes multiple strategies, including sequestration in lipid vesicles, to raise the rate and specificity of chemical reactions through increases in effective molarity of reactants. We show that micelle-assisted reaction can facilitate native chemical ligations (NCLs) between a peptide-thioester - in which the thioester leaving group contains a lipid-like alkyl chain - and a Cys-peptide modified by a lipid-like moiety. Hydrophobic lipid modification of each peptide segment promotes the formation of mixed micelles, bringing the reacting peptides into close proximity and increasing the reaction rate. The approach enables the rapid synthesis of polypeptides using low concentrations of reactants without the need for thiol catalysts. After NCL, the lipid moiety is removed to yield an unmodified ligation product. This micelle-based methodology facilitates the generation of natural peptides, like Magainin 2, and the derivatization of the protein Ubiquitin. Formation of mixed micelles from lipid-modified reactants shows promise for accelerating chemical reactions in a traceless manner. Sequestration of reactants in lipid vesicles is a strategy prevalent in biological systems to raise the rate and specificity of chemical reactions. Here, the authors show that micelle-assisted reactions facilitate native chemical ligation between a peptide-thioester and a Cys-peptide modified by a lipid-like moiety.