Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal Immunotherapy for Drug-Resistant Enterobacteriaceae

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 n...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie 2015-09, Vol.127 (37), p.11103-11107
Main Authors: Liu, Lin, Zha, Jingying, DiGiandomenico, Antonio, McAllister, Douglas, Stover, C. Kendall, Wang, Qun, Boons, Geert-Jan
Format: Article
Language:English
Subjects:
Antigene
Antigens
Carboxylic acids
Chemistry
Enterobacteriaceae
Enterobakterien
Glykosylierungen
Immunotherapy
Immuntherapie
Monoclonal antibodies
Monosaccharides
Oligosaccharide
Oligosaccharides
Polysaccharides
Synthesis (chemistry)
Time measurements
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Alle Enterobakterien exprimieren das Polysaccharid ECA („enterobacterial common antigen”︁), das eine attraktive Zielstruktur für die Entwicklung von universellen Immuntherapien ist. Von ECA abgeleitete Oligosaccharide wurden chemisch synthetisiert und genutzt, um immundominante Epitope zu identifizieren und einen monoklonalen Antikörper mit breiter Enterobakterien‐Erkennung zu entwickeln.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201505420