Key Laboratory of Polymeric Materials and Application Technology of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan, Hunan 411105, China.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Biomacromolecules. 2021 Jun 14;22(6):2373-2381. doi: 10.1021/acs.biomac.1c00126. Epub 2021 May 6.
Antimicrobial polypeptides are promising mimics of antimicrobial peptides (AMPs) with low risks of antimicrobial resistance (AMR). Polypeptides with facile and efficient production, high antimicrobial activity, and low toxicity toward mammalian cells are highly desirable for practical applications. Herein, triblock copolypeptides with chloro groups (PPG-PCPBLG) and different main-chain lengths were synthesized via an ultrafast ring-opening polymerization (ROP) using a macroinitiator, namely poly(propylene glycol) bis(2-aminopropyl ether), and purified or nonpurified monomer (i.e., CPBLG-NCA). PPG-PCPBLG with 90 amino acid residues can be readily prepared within 300 s. Imidazolium-based block copolypeptides (PPG-PIL) were facilely prepared via nucleophilic substitution of PPG-PCPBLG with NaN and subsequent "click" chemistry. α-Helical PPG-PIL can self-assemble into nanostructured and cationic micelles which displayed highly potent antimicrobial activity and low hemolysis. The top-performing material, namely PPG-PIL, showed low minimum inhibitory concentration (MIC) against both Gram-positive and Gram-negative (25 μg mL). It also displayed low toxicity against mouse embryonic fibroblast (NIH 3T3) and human embryonic kidney (293T) cells at 2× MIC.
抗菌多肽是有前景的抗菌肽 (AMPs) 模拟物，其抗菌耐药性 (AMR) 的风险较低。具有易于生产、高效抗菌活性和低细胞毒性的多肽对于实际应用是非常理想的。本文通过使用大分子引发剂，即聚丙二醇双(2-氨基丙基醚)，以及纯化或未纯化的单体（即 CPBLG-NCA），通过超快开环聚合 (ROP) 合成了具有氯基团的嵌段共多肽 (PPG-PCPBLG) 和不同的主链长度。含有 90 个氨基酸残基的 PPG-PCPBLG 可以在 300 s 内轻易制备。通过 PPG-PCPBLG 与 NaN 的亲核取代反应和随后的“点击”化学，可以轻易地制备出基于咪唑的嵌段共多肽 (PPG-PIL)。α-螺旋 PPG-PIL 可以自组装成具有纳米结构和阳离子性的胶束，显示出高效的抗菌活性和低溶血。表现最好的材料，即 PPG-PIL，对革兰氏阳性菌和革兰氏阴性菌的最低抑菌浓度 (MIC) 均较低（均为 25 μg mL）。在 2×MIC 下，它对小鼠胚胎成纤维细胞 (NIH 3T3) 和人胚肾 (293T) 细胞的毒性也较低。
