Abstract In this study, a Gram positive bacteria effective antibiotic, vancomycin (VAN), was conjugated with antimicrobial cationic polymers (ACPs) that were found to be active against both Gram positive and Gram negative bacteria previously, and the antibacterial activity of newly synthesized VAN-PEG-ACP conjugates were investigated. VAN was first PEGylated using Michael Addition method, then the ACPs, which were synthesized using ring-opening metathesis polymerization (ROMP), were bound covalently to the VAN-PEG structure using cross metathesis pathways and thus cationic polymer-vancomycin conjugates (VAN-PEG-ACPs) were obtained. The antimicrobial activity of the conjugates were investigated against Gram negative strain E. coli and Gram positive strains S. aureus and E. feacalis. Con_1_10k_1, Con_2a_3k_1, and Con_2b_3k_1 were found to be active towards S. aureus (MIC= 64 µg/ml, 32 µg/mL, and 32 µg/mL, respectively) and Con_2a_3k_1, and Con_2b_3k_1 were found to be active also towards E. feacalis (MIC= 16 µg/ml and 32 µg/mL, respectively), however they did not show activity towards E. coli. All the conjugates were found to be non-hemolytic towards red blood cells (HC50 = >1024 µg/mL). MTS assay results also showed that the conjugates did not lyse viable HUVEC cells within 72 hours. The membrane deformation of S. aureus was monitored using scanning electron microscopy (SEM) techniques in the presence of the polymers and the conjugates.

中文翻译：

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阳离子聚合物-万古霉素偶联物的抗菌和溶血活性

摘要 在这项研究中，一种革兰氏阳性菌有效抗生素万古霉素 (VAN) 与抗菌阳离子聚合物 (ACPs) 结合，该聚合物先前发现对革兰氏阳性菌和革兰氏阴性菌均有活性，新合成的 VAN 具有抗菌活性。研究了-PEG-ACP缀合物。VAN 首先使用迈克尔加成法进行聚乙二醇化，然后使用开环复分解聚合 (ROMP) 合成的 ACP 使用交叉复分解途径共价结合到 VAN-PEG 结构上，因此阳离子聚合物-万古霉素缀合物 (VAN-PEG) -ACP）。研究了缀合物对革兰氏阴性菌株大肠杆菌和革兰氏阳性菌株金黄色葡萄球菌和粪肠球菌的抗微生物活性。Con_1_10k_1、Con_2a_3k_1、发现 Con_2b_3k_1 和 Con_2b_3k_1 对金黄色葡萄球菌有活性（MIC 分别为 64 µg/ml、32 µg/mL 和 32 µg/mL），发现 Con_2a_3k_1 和 Con_2b_3k_1 也对粪肠球菌（MIC=分别为 16 µg/ml 和 32 µg/mL），但是它们对大肠杆菌没有表现出活性。发现所有缀合物对红细胞均不溶血 (HC50 = >1024 µg/mL)。MTS 测定结果还表明，偶联物在 72 小时内不会裂解活的 HUVEC 细胞。在聚合物和缀合物存在下，使用扫描电子显微镜 (SEM) 技术监测金黄色葡萄球菌的膜变形。然而，它们对大肠杆菌没有表现出活性。发现所有缀合物对红细胞均不溶血 (HC50 = >1024 µg/mL)。MTS 分析结果还表明，偶联物在 72 小时内不会裂解活的 HUVEC 细胞。在聚合物和缀合物存在下，使用扫描电子显微镜 (SEM) 技术监测金黄色葡萄球菌的膜变形。然而，它们对大肠杆菌没有表现出活性。发现所有缀合物对红细胞均不溶血 (HC50 = >1024 µg/mL)。MTS 分析结果还表明，偶联物在 72 小时内不会裂解活的 HUVEC 细胞。在聚合物和缀合物存在下，使用扫描电子显微镜 (SEM) 技术监测金黄色葡萄球菌的膜变形。