title: Lipidated cyclic γ-AApeptides display both antimicrobial and anti-inflammatory activity.
abstract: Antimicrobial peptides (AMPs) are host-defense agents capable of both bacterial membrane disruption and immunomodulation. However, the development of natural AMPs as potential therapeutics is hampered by their moderate activity and susceptibility to protease degradation. Herein we report lipidated cyclic γ-AApeptides that have potent antibacterial activity against clinically relevant Gram-positive and Gram-negative bacteria, many of which are resistant to conventional antibiotics. We show that lipidated cyclic γ-AApeptides mimic the bactericidal mechanism of AMPs by disrupting bacterial membranes. Interestingly, they also harness the immune response and inhibit lipopolysaccharide (LPS) activated Toll-like receptor 4 (TLR4) signaling, suggesting that lipidated cyclic γ-AApeptides have dual roles as novel antimicrobial and anti-inflammatory agents.
authors.affiliation: Department of Chemistry, University of South Florida , 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Li
authors.forename: Christina
authors.initials: C
authors.lastname: Smith
authors.forename: Haifan
authors.initials: H
authors.lastname: Wu
authors.forename: Shruti
authors.initials: S
authors.lastname: Padhee
authors.forename: Namitha
authors.initials: N
authors.lastname: Manoj
authors.forename: Joseph
authors.initials: J
authors.lastname: Cardiello
authors.forename: Qiao
authors.initials: Q
authors.lastname: Qiao
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: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D008055:Lipids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051197:Toll-Like Receptor 4