Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, USA.
J Am Chem Soc. 2012 Jul 11;134(27):11088-91. doi: 10.1021/ja303304j. Epub 2012 Jun 27.
A new series of aryl-based synthetic mimics of antimicrobial peptides (SMAMPs) with antimicrobial activity and selectivity have been developed via systematic tuning of the aromatic groups and charge. The addition of a pendant aromatic group improved the antimicrobial activity against Gram-negative bacteria, while the addition of charge improved the selectivity. SMAMP 4 with six charges and a naphthalene central ring demonstrated a selectivity of 200 against both Staphylococcus aureus and Escherichia coli , compared with a selectivity of 8 for the peptide MSI-78. In addition to the direct antimicrobial activity, SMAMP 4 exhibited specific immunomodulatory activities in macrophages both in the presence and in the absence of lipopolysaccharide, a TLR agonist. SMAMP 4 also induced the production of a neutrophil chemoattractant, murine KC, in mouse primary cells. This is the first nonpeptidic SMAMP demonstrating both good antimicrobial and immunomodulatory activities.
现已开发出一系列具有抗菌活性和选择性的新型芳基合成抗菌肽（SMAMP）模拟物，通过系统调整芳基和电荷来实现。引入侧挂芳基可提高抗革兰氏阴性菌的抗菌活性，而引入电荷则可提高选择性。带有六个电荷和萘中环的 SMAMP 4 对金黄色葡萄球菌和大肠杆菌的选择性分别为 200 和 8，而肽 MSI-78 的选择性为 8。除了直接的抗菌活性外，SMAMP 4 在存在和不存在 TLR 激动剂脂多糖的情况下，在巨噬细胞中均表现出特定的免疫调节活性。SMAMP 4 还可诱导小鼠原代细胞中产生中性粒细胞趋化因子，即鼠 KC。这是第一个同时具有良好抗菌和免疫调节活性的非肽 SMAMP。
