Department of Polymer Science & Engineering, University of Massachusetts, Amherst, MA 01003, USA.
Chemistry. 2009 Nov 2;15(43):11710-4. doi: 10.1002/chem.200802558.
We have investigated how doubly selective synthetic mimics of antimicrobial peptides (SMAMPs), which can differentiate not only between bacteria and mammalian cells, but also between Gram-negative and Gram-positive bacteria, make the latter distinction. By dye-leakage experiments on model vesicles and complementary experiments on bacteria, we were able to relate the Gram selectivity to structural differences of these bacteria types. We showed that the double membrane of E. coli rather than the difference in lipid composition between E. coli and S. aureus was responsible for Gram selectivity. The molecular-weight-dependent antimicrobial activity of the SMAMPs was shown to be a sieving effect: while the 3000 g mol(-1) SMAMP was able to penetrate the peptidoglycan layer of the Gram-positive S. aureus bacteria, the 50000 g mol(-1) SMAMP got stuck and consequently did not have antimicrobial activity.
我们研究了双选择性合成抗菌肽模拟物（SMAMPs）如何区分细菌和哺乳动物细胞，以及区分革兰氏阴性菌和革兰氏阳性菌。通过对模型囊泡的染料渗漏实验和对细菌的补充实验，我们能够将革兰氏选择性与这些细菌类型的结构差异联系起来。我们表明，革兰氏选择性的原因是大肠杆菌的双层膜，而不是大肠杆菌和金黄色葡萄球菌之间的脂质组成差异。还表明，SMAMPs 的分子量依赖性抗菌活性是一种筛分效应：虽然 3000 g mol(-1) 的 SMAMP 能够穿透革兰氏阳性金黄色葡萄球菌的肽聚糖层，但 50000 g mol(-1) 的 SMAMP 被卡住，因此没有抗菌活性。
