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   RESEARCH INTERESTS

Research of Dr. Y.A. Knirel is primarily concerned with the chemistry of bacterial surface polysaccharide antigens from the standpoints of elucidation of their structures and correlation between the structure and the immunospecificity. The most projects focus on the determination of full structures of the O-specific polysaccharides of the lipopolysaccharides (O-antigens) and aim at the creation of the chemical basis for the classification of the bacteria. The core and lipid A regions of the lipopolysaccharides are studied for the chemotaxonomic purposes and with the goal of elucidating how their structural features contribute to the biological properties and functioning of the lipopolysaccharide molecule. These data are critical for understanding mechanisms of infection pathogenesis and development of new diagnostic agents and therapeutics against pathogens. Directed chemical modifications of certain polysaccharides and lipopolysaccharides are performed in an effort to construct a new generation of conjugate vaccines.

Reserach interests of Dr. Y.A. Knirel include studies of the lipopolysaccharides of medically important Gram-negative bacteria, including Pseudomonas aeruginosa, Aeromonas hydrophila, enteric bacteria Proteus, Providencia, Hafnia, Citrobacter, Salmonella, Escherichia and Shigella, the gastric bacterium Helicobacter pylori, the Legionnaire's disease bacterium Legionella pneumophila, the cause of plague Yersinia pestis, as well as phytopathogenic bacteria (Erwinia, Pseudomonas syringae, Xanthomonas campestris) and marine bacteria (Shewanella, Pseudoalteromonas). Determination of the O-antigen structures combined with gene sequencing enable elucidation of the gene functions and the evolutionary history of the O-antigen gene clusters of Escherichia coli and Shigella. Discovery of variations in the lipopolysaccharide structures of Helicobacter pylori and Yersinia pestis depending on the environmental conditions shed light on the role of the lipopolysaccharide as a virulence factor of the bacteria.

In the polysaccharides studied, Dr. Y.A. Knirel and his coworkers have identified a number of new sugars and non-sugar components, including 2,3-diamino-2,3-dideoxyhexuronic acids and 5,7-diamino-3,5,7,9-tetradeoxynonulosonic acids, higher branched monosaccharides, N-substituents of amino sugars, such as (R)- and (S)-3-hydroxybutyryl groups and an acetimidoyl group, compounds linked via phosphate groups (e.g., 2-[(R)-1-carboxyethylamino]ethanol) and carboxyl groups of hexuronic acids (N^e-[(R)- and (S)-1-carboxyethyl)]-L-lysine). New chemical approaches to structural analysis of complex polysaccharides have been elaborated, including selective cleavage of glycosidic linkages using solvolysis with anhydrous hydrogen fluoride and trifluoromethanesulfonic (triflic) acid. In cooperation with Dr. A.S. Shashkov and Dr. G.M. Lipkind, new methods for determination of the absolute configurations of monosaccharides and elucidation of structures of regular polysaccharides have been developed based on regularities in ¹³C-NMR chemical shifts.

Y.A. Knirel works on the construction of pathogen glycoarray as a resource for studies of interactions of proteins with carbohydrates of medically important bacteria, including polysaccharide and oligosaccharide chains of lipopolysaccharides. It will provide a tool for easy detection of specific antibodies (immunoglobulins) and profiling the bacterial carbohydrates specificity for lectins as well as for reliable serodiagnostics and seroepidemiology of infectious diseases. Internet-based Bacterial Carbohydrate Structure DataBase (BCSDB) is being developed with the aim to collect and to make available via Internet information on all bacterial carbohydrates with known structure.

   Main reserach projects, collaborators, and funding sources

   Selected publications

   All publications

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