Zheng Botuo, Bai Tianwen, Ling Jun, Sun Jihong
Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
Commun Chem. 2020 Oct 28;3(1):144. doi: 10.1038/s42004-020-00393-y.
Synthesis of poly(α-amino acid)s bearing carboxyl groups is a critical pathway to prepare biomaterials to simulate functional proteins. The traditional approaches call for carboxyl-protected monomers to prevent degradation of monomers or wrong linkage. In this contribution, we synthesize N-carboxypentyl glycine N-thiocarboxyanhydride (CPG-NTA) and iminodiacetic acid N-thiocarboxyanhydride (IDA-NTA) without protection. Initiated by amines, CPG-NTA directly polymerizes into polyCPG bearing unprotected carboxyl groups with controlled molecular weight (2.8-9.3 kg mol) and low dispersities (1.08-1.12). Block and random copolymerizations of CPG-NTA with N-ethyl glycine N-thiocarboxyanhydride (NEG-NTA) demonstrate its versatile construction of complicated polypeptoids. On the contrary, IDA-NTA transforms amines into cyclic IDA dimer-capped species with carboxyl end group in decent yields (>89%) regio-selectively. Density functional theory calculation elucidates that IDA repeating unit is prone to cyclize to be the six-membered ring product with low ΔG. The polymer is a good adhesive reagent to various materials with adhesive strength of 33-229 kPa.
合成带有羧基的聚（α-氨基酸）是制备模拟功能蛋白的生物材料的关键途径。传统方法需要使用羧基保护的单体来防止单体降解或错误连接。在本研究中，我们合成了未受保护的N-羧基戊基甘氨酸N-硫代羧基酐（CPG-NTA）和亚氨基二乙酸N-硫代羧基酐（IDA-NTA）。在胺引发下，CPG-NTA直接聚合成带有未保护羧基的聚CPG，分子量可控（2.8 - 9.3 kg/mol）且分散度低（1.08 - 1.12）。CPG-NTA与N-乙基甘氨酸N-硫代羧基酐（NEG-NTA）的嵌段和无规共聚展示了其构建复杂聚肽的多功能性。相反，IDA-NTA能将胺区域选择性地转化为带有羧基端基的环状IDA二聚体封端物种，产率良好（>89%）。密度泛函理论计算表明，IDA重复单元易于环化形成具有低吉布斯自由能变化的六元环产物。该聚合物对各种材料是一种良好的粘合剂，粘合强度为33 - 229 kPa。
