Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Department of Chemistry, University of Southern California, Los Angeles, CA, 90089, USA.
Nat Commun. 2020 Jun 3;11(1):2793. doi: 10.1038/s41467-020-16595-w.
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.
生物学利用多种策略，包括将反应物隔离在脂质小泡中，通过提高反应物的有效摩尔浓度来提高化学反应的速度和特异性。我们表明，胶束辅助反应可以促进肽硫酯（其中硫酯离去基团含有类脂烷基链）与通过类脂部分修饰的 Cys-肽之间的天然化学连接（NCL）。每个肽段的疏水性脂质修饰促进了混合胶束的形成，使反应肽彼此靠近，并提高了反应速率。该方法可在不使用硫醇催化剂的情况下，使用低浓度的反应物快速合成多肽。NCL 后，去除脂质部分以得到未修饰的连接产物。这种基于胶束的方法有助于生成天然肽，如 Magainin 2，以及蛋白质泛素的衍生化。由脂质修饰反应物形成的混合胶束有望以无痕迹的方式加速化学反应。
