CAS Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, Jilin, P. R. China.
University of Science and Technology of China, Hefei 230026, Anhui, P. R. China.
Biomacromolecules. 2021 Sep 13;22(9):3992-4003. doi: 10.1021/acs.biomac.1c00785. Epub 2021 Aug 17.
Thermosensitive polypeptide hydrogels have gained considerable attention in potential biomedical applications, of which the polymer structure may be tuned by residue chirality. In this study, polypeptide-based block copolymers with different chiralities were synthesized by ring-opening polymerization of γ-ethyl-l-glutamate -carboxyanhydride and/or γ-ethyl-d-glutamate -carboxyanhydride using amino-terminated monomethoxy poly(ethylene glycol) as a macroinitiator. All mPEG-polypeptide copolymers underwent sol-gel transition with an increase in temperature. The block copolymers with mixed enantiomeric residues of γ-ethyl-l-glutamate (ELG) and γ-ethyl-d-glutamate (EDG) in the polypeptide blocks exhibited lower critical gelation concentrations and lower critical gelation temperatures compared with those composed of pure ELG or EDG residues. We established that the difference in gelation properties between the copolymers was derived from the distinction of the secondary structures. We further demonstrated the influence of polypeptide chirality on the degradability and biocompatibility of hydrogels . Our findings provide insights into the design of hydrogels having tailored secondary conformation, gelation property, and biodegradability.
温敏多肽水凝胶在潜在的生物医学应用中引起了相当大的关注，其中聚合物结构可以通过残基手性进行调节。在这项研究中，通过使用端氨基单甲氧基聚乙二醇（mPEG）作为大分子引发剂，对 γ-乙基-l-谷氨酸-羧酸酐和/或 γ-乙基-d-谷氨酸-羧酸酐开环聚合，合成了具有不同手性的多肽基嵌段共聚物。所有 mPEG-多肽共聚物的温度升高时都会发生溶胶-凝胶转变。与由纯 ELG 或 EDG 残基组成的嵌段共聚物相比，在多肽嵌段中具有混合对映体的 γ-乙基-l-谷氨酸（ELG）和 γ-乙基-d-谷氨酸（EDG）残基的嵌段共聚物具有更低的临界凝胶浓度和更低的临界凝胶温度。我们确定了共聚物之间凝胶性质的差异源自于二级结构的差异。我们进一步证明了多肽手性对水凝胶降解性和生物相容性的影响。我们的研究结果为设计具有定制的二级构象、凝胶性质和生物可降解性的水凝胶提供了新的思路。
