State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, School of Biomedical Sciences, Hunan University, Changsha, Hunan, 410082, China.
Wenzhou Institute, University of Chinese Academy Sciences, Wenzhou, Zhejiang, 325000, China.
Angew Chem Int Ed Engl. 2022 Nov 2;61(44):e202212829. doi: 10.1002/anie.202212829. Epub 2022 Oct 5.
Disulfide bond formation is a common mechanism for regulating conformational changes in proteins during oxidative folding. Despite extensive studies of the use of multiple disulfide bonds to constrain peptide conformation, few studies have explored their usage in developing self-assembling peptides. Herein, we report that a thiol-rich peptide could fold into an amphiphilic β-hairpin conformation through the formation of two hetero-disulfide bonds upon oxidation, subsequently self-assembling into a mechanically rigid hydrogel. Breaking disulfide bonds under reductive condition, the hydrogel exhibited a transition from hydrogel to solution. Molecular simulation revealed that intermolecular interaction between two tryptophan residues was indispensable for hydrogelation. This work is the first case of the use of multiple disulfide bonds to control conformational change and self-assembly, and provides a cell-compatible hydrogel material for potential biomedical application.
二硫键的形成是一种常见的调节蛋白质在氧化折叠过程中构象变化的机制。尽管已经广泛研究了使用多个二硫键来约束肽构象，但很少有研究探索它们在开发自组装肽中的应用。在这里，我们报告说，富含巯基的肽可以通过氧化形成两个杂二硫键折叠成两亲性β发夹构象，随后自组装成机械刚性水凝胶。在还原条件下打破二硫键，水凝胶表现出从水凝胶到溶液的转变。分子模拟表明，两个色氨酸残基之间的分子间相互作用对于水凝胶化是必不可少的。这项工作是首次使用多个二硫键来控制构象变化和自组装，并为潜在的生物医学应用提供了一种细胞相容的水凝胶材料。
