Synthese von Acinetobacter LPS Liganden für Collectine
- Lebensmittel, Ernährung, Gesundheit
- Biotechnologie
Abstract
Lectins, which constitute important components of the innate mammalian immune system, bind to manifold carbohydrate ligands exposed on the cell surface of pathogenic fungi, bacteria and viruses. The group of C-reactive lectins requires the presence of calcium ions for the binding to the hydroxyl groups of carbohydrates. Prominent examples of these lectins are the mannose-binding protein (MBL) and the lung surfactant proteins SP-A and SP-D, which induce immediate immune reactions upon contact with microbes in the serum and at the surface-layer of lung tissue. The weak individual sugar-lectin binding interactions are strongly enhanced due to multivalent presentation of the carbohydrate ligands at the cell surface. Previous studies have shown, that surface structures of Acinetobacter bbind with unusual high affinity to the murine mannose-binding protein MBL-A. Since the binding region is not known in molecular detail and carbohydrate fractions from bacterial lipopolysaccharide (LPS) may only be isolated in small amounts and insufficient purity, chemical synthesis of defined subunits will be performed. The synthesis is based on the core region of bacterial lipopolysaccharide from Acinetobacter haemolyticus, a member of a bacterial genus causing severe nosocomial infections and being notoriously resistant to antibiotic therapies. The proposal aims at the preparation of oligosaccharides up to the pentasaccharide level containing a specific phosphate groups as well octulosonic sugar acids (Kdo, Ko), improving synthetic strategies for the synthesis of Ko and Ko glycosyl donors and investigating glycoside coupling reactions under batch and microfluidic conditions. The compounds have been designed as monovalent glycosides, as multivalent assemblies and as neoglycoproteins. The products will then be used for binding studies with MBL-A, SP-A and SP-D in order to define the topology of the carbohydrate recognition on a molecular basis. The molecular details will be elucidated by binding and crystallographic studies within established long-standing cooperations with groups in Germany, Canada and the US and will include lectin-binding assays tests, surface-plasmon resonance studies and isothermal microcalorimetric measurements. As complementary techniques, molecular modeling and NMR spectroscopic techniques will be used. The outcome of the project should contribute to a better understanding of bacterial carbohydrate-lectin interaction with charged sugar ligands and translate into novel approaches towards the development of anti-inflammatory agents to be used in anti-inflammatory and antiallergic therapies.
katalog.ub.tuwien.ac.atProject staff
Paul Kosma
Univ.-Prof. i.R. Dipl.-Ing.Dr.techn. Paul Kosma
paul.kosma@boku.ac.at
Tel: +43 1 47654-77355
BOKU Project Leader
15.09.2012 - 14.05.2016
Andreas Hofinger-Horvath
Ass.Prof.i.R. Dipl.-Ing.Dr.nat.techn. Andreas Hofinger-Horvath
andreas.hofinger@boku.ac.at
Tel: +43 1 47654-77381
Project Staff
15.09.2012 - 14.05.2016
BOKU partners
External partners
Forschungszentrum Borstel
Sven Mueller-Loennies
partner
University of Victoria
Stephen V. Evans
partner
Boston University
James Head
partner