Biomimetic Glycosylated Polythreonines by N -Carboxyanhydride Polymerization
Biomimetic Glycosylated Polythreonines by N -Carboxyanhydride Polymerization
复制标题
N-羧酸酐聚合仿生糖基化聚苏氨酸
DOI：
10.1021/acs.biomac.2c00020
复制
发表时间：
2022
影响因子：
6.2
通讯作者：
Kramer, Jessica R.
中科院分区：
文献类型：
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作者：
Deleray, Anna C.;Kramer, Jessica R.
糖基化苏氨酸 (Thr) 是一种在看似不同的天然蛋白质（从深海胶原蛋白到粘蛋白）中发现的结构基序。这些重要蛋白质的合成模拟物在生物医学中引起了极大的兴趣。此类材料还提供了以受控和可调的方式探究单个氨基酸对蛋白质结构的贡献的便捷途径。N-羧酸酐（NCA）聚合是此类仿生多肽的一种主要途径。然而，Thr NCA 的制备和聚合方面的挑战阻碍了此类结构的获得。在这里，我们提出了几种高分析纯度的糖基化和乙酰化 Thr NCA 的优化路线。过渡金属催化产生了具有可预测链长和低分散性的可调节同源、统计和嵌段多肽。我们进行了结构研究来检查它们的水构象，发现高含量的游离 OH Thr 会诱导不溶于水的 β-折叠的形成。然而，糖基化似乎会诱导聚脯氨酸 II 型螺旋构象，这揭示了糖苏氨酸在粘蛋白和胶原蛋白等刚性蛋白中的作用。
Glycosylated threonine (Thr) is a structural motif found in seemingly disparate natural proteins from deep-sea collagen to mucins. Synthetic mimics of these important proteins are of great interest in biomedicine. Such materials also provide ready access to probe the contributions of individual amino acids to protein structure in a controlled and tunable manner.N-Carboxyanhydride (NCA) polymerization is one major route to such biomimetic polypeptides. However, challenges in the preparation and polymerization of Thr NCAs have impeded obtaining such structures. Here, we present optimized routes to several glycosylated and acetylated Thr NCAs of high analytical purity. Transition metal catalysis produced tunable homo-, statistical, and block-polypeptides with predictable chain lengths and low dispersities. We conducted structural work to examine their aqueous conformations and found that a high content of free OH Thr induces the formation of water-insoluble β-sheets. However, glycosylation appears to induce a polyproline II-type helical conformation, which sheds light on the role of glyco-Thr in rigid proteins such as mucins and collagen.