Alternating polypeptoids are particularly appealing because alternating sequence may impart highly ordered structure and special functions, while their simple synthesis still remains a key challenge. We describe that natural amino acid monomers can be polymerized via Ugi reaction in a step-growth fashion as an AA′ BB′ system, which leads to alternating polypeptoids with molecular weight up to 15 kg/mol. These alternating polypeptoids are thermally responsive and exhibit cloud points (T_cp) between 27 and 37 °C. Importantly, the marriage of high functionality of amino acids with Ugi reaction also enables the preparation of polypeptoids encoding both protected amino and carboxyl groups in the side chains with alternating arrangement. The cleavage of the protecting groups leads to alternating polyampholytes without any compositional drift. Such alternating polyampholytes not only exhibit high water solubility (>100 mg/mL) but also demonstrate the ability to resist aggregation with proteins. Moreover, the cell viability measurements reveal that these materials have minimal cytotoxicity to HeLa cells. Overall, this study offers us a simple way to prepare a variety of polypeptoids and polyampholytes as new protein-resistant materials for bioapplications.

中文翻译：

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交替多肽和多两性蛋白作为抗蛋白质聚合物的合成及性能

交替的多肽类特别吸引人，因为交替的序列可能赋予高度有序的结构和特殊功能，而它们的简单合成仍然是关键的挑战。我们描述了天然氨基酸单体可以通过Ugi反应以AA'BB'系统的逐步增长方式聚合，从而产生分子量高达15 kg / mol的交替多肽。这些交替的多肽分子具有热响应性，并表现出浊点（T _cp）在27至37°C之间。重要的是，氨基酸的高官能度与Ugi反应的结合还使得能够制备以交替排列方式编码侧链中受保护的氨基和羧基的多肽类。保护基的裂解导致交替的多两性电解质，而没有任何组成漂移。这种交替的多两性电解质不仅表现出高水溶性（> 100 mg / mL），而且还表现出抵抗蛋白质聚集的能力。此外，细胞活力的测量结果表明，这些物质对HeLa细胞的细胞毒性极小。总的来说，这项研究为我们提供了一种简单的方法来制备多种多肽类和两性电解质，作为生物应用中的新型抗蛋白材料。