title: The development of antimicrobial a-AApeptides that suppress proinflammatory immune responses.
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.
authors.forename: Shruti
authors.initials: S
authors.lastname: Padhee
authors.forename: Christina
authors.initials: C
authors.lastname: Smith
authors.forename: Haifan
authors.initials: H
authors.lastname: Wu
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Li
authors.forename: Namitha
authors.initials: N
authors.lastname: Manoj
authors.forename: Qiao
authors.initials: Q
authors.lastname: Qiao
authors.forename: Zoya
authors.initials: Z
authors.lastname: Khan
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Cao
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D057809:HEK293 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D057786:Peptidomimetics / Q000737:chemistry* / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D010456:Peptides, Cyclic; D057786:Peptidomimetics; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4