title: Total Synthesis of Five Lipoteichoic acids of Clostridium difficile.
abstract: The emergence of hypervirulent resistant strains have made Clostridium difficile a notorious nosocomial pathogen and has resulted in a renewed interest in preventive strategies, such as vaccines based on (synthetic) cell wall antigens. Recently, the structure of the lipoteichoic acid (LTA) of this species has been elucidated. Additionally, this LTA was found to induce the formation of protective antibodies against C. difficile in rabbits and mice. The LTA from C. difficile is isolated as a microheterogenous mixture, differing in size and composition, impeding any structure-activity relationship studies. To ensure reliable biological results, pure and well-defined synthetic samples are required. In this work the total synthesis of LTAs from C. difficile with defined chain length is described and the initial biological results are presented.
authors.affiliation: Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen Ø (Denmark).
authors.forename: Wouter F J
authors.initials: WF
authors.lastname: Hogendorf
authors.forename: Nicolas
authors.initials: N
authors.lastname: Gisch
authors.forename: Dominik
authors.initials: D
authors.lastname: Schwudke
authors.forename: Holger
authors.initials: H
authors.lastname: Heine
authors.forename: Mikael
authors.initials: M
authors.lastname: Bols
authors.forename: Christian Marcus
authors.initials: CM
authors.lastname: Pedersen
mesh_terms: D016360:Clostridioides difficile / Q000737:chemistry*; D004761:Enterocolitis, Pseudomembranous / Q000382:microbiology*; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013682:Teichoic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid
keywords: Clostridium difficile; Gram-positive bacteria; glycolipids; lipoteichoic acid; total synthesis