Zhang Xiaojie, Wang Shixue, Liu Jing, Xie Zhigang, Luan Shifang, Xiao Chunsheng, Tao Youhua, Wang Xianhong
University of Chinese Academy of Sciences, Beijing 100039, People's Republic of China.
ACS Macro Lett. 2016 Sep 20;5(9):1049-1054. doi: 10.1021/acsmacrolett.6b00530. Epub 2016 Aug 30.
Polypeptoids represent a significant class of synthetic analogues of natural polypeptides with potential biomimetic applications in materials, catalysis, and pharmaceuticals, but their simple and general synthesis still remains a key challenge. Herein, we demonstrate that Ugi reaction of natural amino acids leads to structurally diverse polypeptoids, including γ- and δ-, as well as poly(ε-peptoid)s, under mild conditions (open to air, room temperature, and catalyst free). Moreover, this strategy also offers manifold opportunities to introduce functional groups such as fluorescent and clickable alkenes groups into polypeptoids. Such poly(ε-peptoid)s not only exhibit good biocompatibility and antibacterial activity, but perform very effectively as a drug-delivery system. The bacterial inhibition rate of poly(ε-peptoid) was up to 88.8% at concentration of 20 μg mL in comparison to 61.8% of the poly(ε-lysine) control. Overall, this study offers us a general methodology toward facile preparation of polypeptoids for bioapplications.
聚肽类似物是天然多肽的一类重要合成类似物，在材料、催化和制药领域具有潜在的仿生应用，但它们的简单通用合成仍然是一个关键挑战。在此，我们证明天然氨基酸的乌吉反应在温和条件下（暴露于空气中、室温且无催化剂）可生成结构多样的聚肽类似物，包括γ-和δ-聚肽类似物以及聚（ε-聚肽类似物）。此外，该策略还提供了多种机会将诸如荧光和可点击烯烃基团等官能团引入聚肽类似物中。此类聚（ε-聚肽类似物）不仅表现出良好的生物相容性和抗菌活性，而且作为药物递送系统表现非常有效。与聚（ε-赖氨酸）对照的61.8%相比，聚（ε-聚肽类似物）在浓度为20 μg/mL时的细菌抑制率高达88.8%。总体而言，本研究为我们提供了一种简便制备用于生物应用的聚肽类似物的通用方法。
