Chembiochem. 2014 Mar 21;15(5):688-94. doi: 10.1002/cbic.201300709.
Herein we describe the development of a new class of antimicrobial and anti-inflammatory peptidomimetics: cyclic lipo-α-AApeptides. They have potent and broad-spectrum antibacterial activity against a range of clinically relevant pathogens, including both multidrug-resistant Gram-positive and Gram-negative bacteria. Fluorescence microscopy suggests that cyclic lipo-α-AApeptides kill bacteria by disrupting bacterial membranes, possibly through a mechanism similar to that of cationic host-defense peptides (HDPs). Furthermore, the cyclic lipo-α-AApeptide can mimic cationic host-defense peptides by antagonizing Toll-like receptor 4 (TLR4) signaling responses and suppressing proinflammatory cytokines such as tumor necrosis factor-α (TNF-α). Our results suggest that by mimicking HDPs, cyclic lipo-α-AApeptides could emerge as a new class of antibiotic agents that directly kill bacteria, as well as novel antiinflammatory agents that act through immunomodulation.
在这里，我们描述了一类新型的抗菌和抗炎肽模拟物：环状脂肽-α-AA 肽。它们对一系列临床相关病原体具有强大且广谱的抗菌活性，包括多种耐药性革兰氏阳性和革兰氏阴性细菌。荧光显微镜观察表明，环状脂肽-α-AA 肽通过破坏细菌膜来杀死细菌，其作用机制可能类似于阳离子宿主防御肽（HDP）。此外，环状脂肽-α-AA 肽可以通过拮抗 Toll 样受体 4（TLR4）信号转导反应并抑制肿瘤坏死因子-α（TNF-α）等促炎细胞因子来模拟阳离子宿主防御肽。我们的结果表明，通过模拟 HDP，环状脂肽-α-AA 肽可能成为一类新型的抗生素药物，既能直接杀死细菌，又能通过免疫调节发挥抗炎作用。
