Chemical synthesis can produce water-soluble globular proteins bearing specifically designed modifications. These synthetic molecules have been used to study the biological functions of proteins and to improve the pharmacological properties of protein drugs. However, the above advances notwithstanding, membrane proteins (MPs), which comprise 20–30% of all proteins in the proteomes of most eukaryotic cells, remain elusive with regard to chemical synthesis. This difficulty stems from the strong hydrophobic character of MPs, which can cause considerable handling issues during ligation, purification, and characterization steps. Considerable efforts have been made to improve the solubility of transmembrane peptides for chemical ligation. These methods can be classified into two main categories: the manipulation of external factors and chemical modification of the peptide. This Account summarizes our research advances in the development of chemical modification especially the two generations of removable backbone modification (RBM) strategy for the chemical synthesis of MPs.

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化学合成膜蛋白的可移动骨干修饰方法

化学合成可以产生带有特殊设计修饰的水溶性球状蛋白。这些合成分子已用于研究蛋白质的生物学功能并改善蛋白质药物的药理特性。但是，尽管取得了上述进展，但在大多数真核细胞蛋白质组中，蛋白质占所有蛋白质的20％至30％的膜蛋白（MPs）在化学合成方面仍然难以捉摸。这种困难源于MP的强疏水特性，在连接，纯化和表征步骤中会引起相当大的处理问题。为了提高跨膜肽在化学连接中的溶解度，已经做出了相当大的努力。这些方法可以分为两个主要类别：外部因素的操纵和肽的化学修饰。此帐户总结了我们在化学修饰开发方面的研究进展，特别是MP的化学合成的两代可移动骨架修饰（RBM）策略。