The Section works on the interaction of (complex) carbohydrate immuno- determinants with monoclonal antibodies (MAbs). The elucidation of this interaction in great molecular detail pertains to all ligand-protein interactions. We are executing: 1. Physico-chemical studies on antibody/antigen systems (Sh. dys. type 1, V. cholera). 2. The synthesis of ligands for affinity studies. 3. The study of immunodeterminants of bacteria causing significant diseases on a global scale (Sh. dysenteriae type 1, V. cholera), so as to evaluate procedures for vaccine development. 4. The amino acid sequencing of immunoglobulins and studies on their tertiary structures. We are continuing to determine the specific interaction between microbial polysaccharides, such as dextran and a number of monoclonal antibodies, Vibrio cholera and its monoclonal antibodies, and have prepared ligands to probe the fundamental nature of these antibody-antigen association. We have prepared additional complex fragments of the capsular polysaccharide of Shigella dysenteriae type 1 by sophisticated syntheses. These include deoxy and deoxyfluoro derivatives of the determinant. Studies are continuing on the binding area of a monoclonal antibodies towards this disease-causing micro-organism. The amino acid sequence of some of these antibodies will be determined by cDNA approaches. Three dimensional structures will be evaluated to delineate actual molecular forces involved in the binding.

Project Start
Project End
Budget Start
Budget End
Support Year
21
Fiscal Year
1994
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Hou, Shu-jie; Kovac, Pavol (2010) Enhanced stereoselectivity of alpha-mannosylation under thermodynamic control using trichloroacetimidates. Carbohydr Res 345:999-1007
Hou, Shu-Jie; Saksena, Rina; Kovac, Pavol (2008) Preparation of glycoconjugates by dialkyl squarate chemistry revisited. Carbohydr Res 343:196-210
Saksena, Rina; Adamo, Roberto; Kovac, Pavol (2007) Immunogens related to the synthetic tetrasaccharide side chain of the Bacillus anthracis exosporium. Bioorg Med Chem 15:4283-310
Wang, Denong; Carroll, Gregory T; Turro, Nicholas J et al. (2007) Photogenerated glycan arrays identify immunogenic sugar moieties of Bacillus anthracis exosporium. Proteomics 7:180-4
Provenzano, Daniele; Kovac, Pavol; Wade, William F (2006) The ABCs (Antibody, B cells, and Carbohydrate epitopes) of cholera immunity: considerations for an improved vaccine. Microbiol Immunol 50:899-927
Ruttens, Bart; Kovac, Pavol (2006) Synthesis of spacer-equipped phosphorylated di-, tri- and tetrasaccharide fragments of the O-specific polysaccharide of Vibrio cholerae O139. Carbohydr Res 341:1077-80
Saksena, Rina; Adamo, Roberto; Kovac, Pavol (2006) Synthesis of the tetrasaccharide side chain of the major glycoprotein of the Bacillus anthracis exosporium. Bioorg Med Chem Lett 16:615-7
Wade, Terri K; Saksena, Rina; Shiloach, Joseph et al. (2006) Immunogenicity of synthetic saccharide fragments of Vibrio cholerae O1 (Ogawa and Inaba) bound to Exotoxin A. FEMS Immunol Med Microbiol 48:237-51
Kovacik, Vladimir; Bekesova, Slavka; Tvaroska, Igor et al. (2006) Positive electrospray ion trap multistage mass spectrometric fragmentation of synthetic analogs of saccharide part of lipopolysaccharides of Vibrio cholerae O:1. J Am Soc Mass Spectrom 17:749-56
Bekesova, Slavka; Kovacik, Vladimir; Chmelik, Josef et al. (2006) Negative electrospray, ion trap multistage mass spectrometry of synthetic fragments of the O-PS of Vibrio cholerae O:1. Eur J Mass Spectrom (Chichester, Eng) 12:43-50

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