Chemical synthesis and biological activity of chlamydial lipopolysaccharide
Abstract
Chlamydiae are intracellular parasitic bacteria which are responsible for manifold acute and chronic diseases in animals and humans. Infections by C. trachomatis affect 500 million people in the developing countries leading to trachoma and blindness, whereas in industrialized countries C. trachomatis is most frequently diagnosed in sexually transmitted diseases. One of the most important discoveries of infectious disease biology in the last decade, however, has been the finding of another chlamydial species (C. pneumoniae) to be associated with cardiovascular diseases, most importantly with atherosclerosis. The proposed project is focused on the chemical synthesis of one of the major antigenic determinants occurring in the outer membrane of the chlamydial cell wall. Since the highly infectious bacteria may only be grown in tissue culture, insufficient amounts of chlamydial components are available for a detailed study of their immunobiological functions. Therefore, chlamydial lipid A will be prepared by chemical synthesis and linked to the genus-specific carbohydrate epitope, which will provide chlamydial lipopolysaccharide in defined and purified form for immunobiological studies. The expected outcome should considerably improve the knowledge on the biological activities of chlamydial endotoxin, its antigenic properties and its biosynthesis. The results may be exploited for better diagnosis of acute and chronic chlamydial infections, lead to potential vaccines or novel antimicrobials by designing proper inhibitors of glycosyl transferases in particular and prove structure - function relationships of endotoxins in general.
Publications
Mapping the binding of synthetic disaccharides representing epitopes of chlamydial lipopolysaccharide to antibodies with NMR.
Autoren: Maaheimo, H; Kosma, P; Brade, L; Brade, H; Peters, T Jahr: 2000
Journal articles
Crystallization and preliminary X-ray diffraction analysis of two homologous antigen-binding fragments in complex with different carbohydrate antigens.
Autoren: Nguyen, HP; Seto, NO; Brade, L; Kosma, P; Brade, H; Evans, SV Jahr: 2001
Journal articles
Germline antibody recognition of distinct carbohydrate epitopes.
Autoren: Nguyen, HP; Seto, NO; MacKenzie, CR; Brade, L; Kosma, P; Brade, H; Evans, SV Jahr: 2003
Journal articles
Hemoglobin enhances the biological activity of synthetic and natural bacterial (endotoxic) virulence factors: a general principle.
Autoren: Howe, J; Richter, W; Hawkins, L; Rössle, M; Alexander, C; Fournier, K; Mach, JP; Waelli, T; Gorczynski, RM; Ulmer, AJ; Brade, H; Zamyatina, A; Kosma, P; Rietschel, ET; Brandenburg, K Jahr: 2008
Journal articles
- external links and characteristics of the publication:
Characterization of high affinity monoclonal antibodies specific for chlamydial lipopolysaccharide.
Autoren: Müller-Loennies, S; MacKenzie, CR; Patenaude, SI; Evans, SV; Kosma, P; Brade, H; Brade, L; Narang, S Jahr: 2000
Journal articles
Synthesis of neoglycoproteins containing Kdo epitopes specific for Chlamydophila psittaci lipopolysaccharide.
Autoren: Kosma, P; Reiter, A; Hofinger, A; Brade, L; Brade, H; Jahr: 2000
Journal articles
A monoclonal antibody recognizing the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) trisaccharide alphaKdo(2-->4)alphaKdo(2-->4)alphaKdo of Chlamydophila psittaci 6BC lipopolysaccharide.
Autoren: Brade, L; Rozalski, A; Kosma, P; Brade, H Jahr: 2000
Journal articles
Synthesis of C-8 deuterated glycosides of 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) related to chlamydial lipopolysaccharide.
Autoren: Kosma, P., Strobl, M., Hofinger, A., Duus, J., Petersen, B.O., Bock, K., Brade, H. Jahr: 2002
Journal articles
A novel strategy for the synthesis of neoglycoconjugates from deacylated deep rough lipopolysaccharides.
Autoren: Müller-Loennies, S; Grimmecke, D; Brade, L; Lindner, B; Kosma, P; Brade, H Jahr: 2002
Journal articles
Synthesis of C-8 deuterated glycosides of 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) related to chlamydial lipopolysaccharide
Autoren: Kosma, P., Strobl, M., Hofinger, A., Duus, J., Petersen, P.O., Bock, K., Brade, H. Jahr: 2002
Monographs
external links and characteristics of the publication:Synthesis of chlamydial tetra- and pentaacyl lipid A
Autoren: Zamyatina, A.; Sekljic, H.; Brade, H.; Kosma, P. Jahr: 2003
Conference & Workshop proceedings, paper, abstract
external links and characteristics of the publication:Synthesis of chlamydial tetra- and penta-acyl lipid A
Autoren: Zamyatina, A., Sekljic, H., Brade, H., Kosma, P. Jahr: 2004
Conference & Workshop proceedings, paper, abstract
external links and characteristics of the publication:Synthesis and purity assessment of tetra- and pentaacyl lipid A of Chlamydia containing (R)-3-hydroxyicosanoic acid
Autoren: Zamyatina, A., Sekljic, H., Brade, H., Kosma, P. Jahr: 2004
Journal articles
Synthesis and antibody recognition of chlamydial lipopolysaccharide
Autoren: Zamyatina, A., Sekljic, H., Brade, H., Evans, S.V., Kosma, P. Jahr: 2005
Conference & Workshop proceedings, paper, abstract
external links and characteristics of the publication:Investigation on the agonistic and antagonistic biological activities of synthetic Chlamydia lipid A and its use in in vitro enzymatic assays.
Autoren: Heine, H; Gronow, S; Zamyatina, A; Kosma, P; Brade, H Jahr: 2007
Journal articles
Project staff
Paul Kosma
Univ.-Prof. i.R. Dipl.-Ing.Dr.techn. Paul Kosma
paul.kosma@boku.ac.at
Tel: +43 1 47654-77355
Project Leader
01.12.1999 - 30.11.2002
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
01.12.1999 - 30.11.2002
Michael Puchberger
Univ.Ass. Mag.rer.nat. Dr.rer.nat. Michael Puchberger
Project Staff
01.12.1999 - 30.11.2002
Alla Zamyatina
Assoc. Prof. Dipl.-Ing.Dr. Alla Zamyatina
alla.zamyatina@boku.ac.at
Tel: +43 1 47654-77384
Project Staff
01.12.1999 - 30.11.2002
BOKU partners
External partners
Forschungszentrum Borstel
none
partner
Institute of Chemistry
none
partner