State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, P. R. China.
Chem Commun (Camb). 2019 Apr 25;55(35):5123-5126. doi: 10.1039/c9cc00401g.
Supramolecular hydrogels of self-assembling peptides and thermogels are very promising for biomedical applications. However, there were no thermogels of self-assembling peptides. In this study, we reported on a novel and versatile strategy to prepare thermogels of self-assembling peptides by enzyme-instructed peptide folding and self-assembly. We synthesized two phosphorylated peptides from insulin growth factor (IGF) and the second mitochondria-derived activator of caspases (Smac) (Nap-FFGGpYGSSSRRAPQT and NBD-GFFpYGAVPIAQK, respectively), which could be converted to possible hydrogelators by enzyme-instructed self-assembly (EISA). We found that EISA using phosphatase at 4 °C resulted in peptides with a random coil conformation, which would self-assemble into worm-like micelles or very short fibers in clear solutions. At a physiological temperature of 37 °C, the peptides would undergo fast transitions from random coil to β-sheet- or α-helix-like conformations, resulting in solution-to-gel transformations. This novel thermogel system was very useful for three-dimensional (3D) cell culture due to the biocompatibility and bioactivity of peptides. Our study provides a novel strategy to prepare a novel thermogel system for biomedical applications.
自组装肽的超分子水凝胶和温敏水凝胶在生物医学应用中非常有前景。然而，目前还没有自组装肽的温敏水凝胶。在这项研究中，我们报告了一种通过酶指导肽折叠和自组装制备自组装肽温敏水凝胶的新策略。我们从胰岛素样生长因子（IGF）和第二线粒体衍生的半胱天冬酶激活剂（Smac）合成了两种磷酸化肽（Nap-FFGGpYGSSSRRAPQT 和 NBD-GFFpYGAVPIAQK），它们可以通过酶指导的自组装（EISA）转化为潜在的水凝胶形成剂。我们发现，在 4°C 下使用磷酸酶进行 EISA 会导致肽呈现无规卷曲构象，在澄清溶液中会自组装成蠕虫状胶束或非常短的纤维。在 37°C 的生理温度下，肽会迅速从无规卷曲转变为β-折叠或α-螺旋样构象，导致溶液到凝胶的转变。由于肽的生物相容性和生物活性，这种新型温敏水凝胶系统非常适用于三维（3D）细胞培养。我们的研究为制备用于生物医学应用的新型温敏水凝胶系统提供了一种新策略。
