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The Development of Antimicrobial α‐AApeptides that Suppress Proinflammatory Immune Responses
Author(s) -
Padhee Shruti,
Smith Christina,
Wu Haifan,
Li Yaqiong,
Manoj Namitha,
Qiao Qiao,
Khan Zoya,
Cao Chuanhai,
Yin Hang,
Cai Jianfeng
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201300709
Subject(s) - proinflammatory cytokine , antimicrobial , tlr4 , peptidomimetic , tumor necrosis factor alpha , bacteria , immune system , biology , microbiology and biotechnology , gram negative bacteria , inflammation , chemistry , immunology , biochemistry , peptide , escherichia coli , gene , genetics
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.