Department of Polymer Science & Engineering, University of Massachusetts, Amherst, MA 01003, USA.
Chemistry. 2009 Nov 2;15(43):11715-22. doi: 10.1002/chem.200900606.
The synthesis and characterization of a series of poly(oxanorbornene)-based synthetic mimics of antimicrobial peptides (SMAMPs) is presented. In the first part, the effect of different organic counterions on the antimicrobial properties of the SMAMPs was investigated. Unexpectedly, adding hydrophobicity by complete anion exchange did not increase the SMAMPs' antimicrobial activity. It was found by dye-leakage studies that this was due to the loss of membrane activity of these polymers caused by the formation of tight ion pairs between the organic counterions and the polymer backbone. In the second part, the effect of molecular charge density on the biological properties of a SMAMP was investigated. The results suggest that, above a certain charge threshold, neither minimum inhibitory concentration (MIC90) nor hemolytic activity (HC50) is greatly affected by adding more cationic groups to the molecule. A SMAMP with an MIC90 of 4 microg mL(-1) against Staphylococcus aureus and a selectivity (=HC50/MIC90) of 650 was discovered, the most selective SMAMP to date.
本文介绍了一系列聚（降冰片烯）基合成抗菌肽模拟物（SMAMPs）的合成与表征。在第一部分中，研究了不同有机抗衡离子对 SMAMPs 抗菌性能的影响。出乎意料的是，通过完全阴离子交换增加疏水性并没有提高 SMAMPs 的抗菌活性。通过染料渗漏研究发现，这是由于有机抗衡离子与聚合物主链之间形成紧密的离子对，导致这些聚合物丧失膜活性。在第二部分中，研究了分子电荷密度对 SMAMP 生物学性质的影响。结果表明，在一定的电荷阈值以上，向分子中添加更多的阳离子基团不会显著影响最小抑菌浓度（MIC90）或溶血活性（HC50）。发现了一种对金黄色葡萄球菌的 MIC90 为 4μg/mL 的 SMAMP，其选择性（=HC50/MIC90）为 650，是迄今为止最具选择性的 SMAMP。
