The Development of Antimicrobial α‐AApeptides that Suppress Proinflammatory Immune Responses |
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Authors: | Shruti Padhee Christina Smith Haifan Wu Yaqiong Li Namitha Manoj Qiao Qiao Zoya Khan Prof. Chuanhai Cao Prof. Hang Yin Prof. Jianfeng Cai |
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Affiliation: | 1. Department of Chemistry, University of South Florida, 4202 E. Fowler Ave, Tampa, FL 33620 (USA);2. Department of Chemistry & Biochemistry and the BioFrontiers Institute, University of Colorado at Boulder, 596 UCB, Boulder, CO 80309‐0596 (USA);3. College of Pharmacy, University of South Florida, 4202 E. Fowler Ave, Tampa, FL 33620 (USA) |
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Abstract: | 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. |
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Keywords: | alpha‐AApeptides anti‐infective activity antimicrobial activity host‐defense peptides peptidomimetics Toll‐like receptors |
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