title: Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal Immunotherapy for Drug-Resistant Enterobacteriaceae.
abstract: All Enterobacteriaceae express a polysaccharide known as enterobacterial common antigen (ECA), which is an attractive target for the development of universally acting immunotherapies. The first chemical synthesis of ECA-derived oligosaccharides for the development of such therapies is described. A number of synthetic challenges had to be addressed, including the development of concise synthetic procedures for unusual monosaccharides, the selection of appropriate orthogonal protecting groups, the development of stereoselective glycosylation methods, appropriate timing for the introduction of the carboxylic acid groups on the ManpNAcA moieties, and the selection of appropriate conditions for the reduction of multiple azido moieties. The synthetic compounds were employed to uncover immunodominant moieties of ECA. Furthermore, a monoclonal antibody (mAb) was developed that binds to ECA and can selectively recognize a wide range of Enterobacteriaceae species.
authors.affiliation: Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, GA 30602 (USA).
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, MD 20878 (USA).
authors.forename: Jingying
authors.initials: J
authors.lastname: Zha
authors.affiliation: Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, MD 20878 (USA).
authors.forename: Antonio
authors.initials: A
authors.lastname: DiGiandomenico
authors.affiliation: Virostat Inc., Portland, ME 04104 (USA).
authors.forename: Douglas
authors.initials: D
authors.lastname: McAllister
authors.affiliation: Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, MD 20878 (USA).
authors.forename: C Kendall
authors.initials: CK
authors.lastname: Stover
authors.affiliation: Department of Infectious Diseases, MedImmune, LLC, Gaithersburg, MD 20878 (USA). wangqu@medimmune.com.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, GA 30602 (USA). gjboons@ccrc.uga.edu.
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Boons
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects; D007167:Immunotherapy
chemical_list: D000942:Antigens, Bacterial; C017286:enterobacterial common antigen
keywords: antigens; enterobacteriaceae; glycosylation; immunotherapy; oligosaccharides