Salas-Ambrosio Pedro, Vexler Shelby, P S Rajalakshmi, Chen Irene A, Maynard Heather D
Department of Chemistry and Biochemistry and California Nano Systems Institute, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California 90095, United States.
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 508 Portola Plaza, Los Angeles, California 90095, United States.
ACS Bio Med Chem Au. 2023 Feb 13;3(2):189-200. doi: 10.1021/acsbiomedchemau.2c00077. eCollection 2023 Apr 19.
One of the primary global health concerns is the increase in antimicrobial resistance. Polymer chemistry enables the preparation of macromolecules with hydrophobic and cationic side chains that kill bacteria by destabilizing their membranes. In the current study, macromolecules are prepared by radical copolymerization of caffeine methacrylate as the hydrophobic monomer and cationic- or zwitterionic-methacrylate monomers. The synthesized copolymers bearing -butyl-protected carboxybetaine as cationic side chains showed antibacterial activity toward Gram-positive bacteria () and Gram-negative bacteria (). By tuning the hydrophobic content, we prepared copolymers with optimal antibacterial activity against , including methicillin-resistant clinical isolates. Moreover, the caffeine-cationic copolymers presented good biocompatibility in a mouse embryonic fibroblast cell line, NIH 3T3, and hemocompatibility with erythrocytes even at high hydrophobic monomer content (30-50%). Therefore, incorporating caffeine and introducing -butyl-protected carboxybetaine as a quaternary cation in polymers could be a novel strategy to combat bacteria.
全球主要的健康问题之一是抗菌药物耐药性的增加。高分子化学能够制备具有疏水和阳离子侧链的大分子，这些大分子通过破坏细菌细胞膜来杀死细菌。在本研究中，通过将甲基丙烯酸咖啡因作为疏水单体与阳离子或两性离子甲基丙烯酸单体进行自由基共聚来制备大分子。合成的带有 -丁基保护的羧酸甜菜碱作为阳离子侧链的共聚物对革兰氏阳性菌（）和革兰氏阴性菌（）均表现出抗菌活性。通过调节疏水含量，我们制备了对包括耐甲氧西林临床分离株在内的具有最佳抗菌活性的共聚物。此外，咖啡因 -阳离子共聚物在小鼠胚胎成纤维细胞系NIH 3T3中表现出良好的生物相容性，并且即使在高疏水单体含量（30 - 50%）下与红细胞也具有血液相容性。因此，在聚合物中引入咖啡因并引入 -丁基保护的羧酸甜菜碱作为季铵阳离子可能是一种对抗细菌的新策略。
