Chemistry of saccharides

N-acetyl-D-glucosamine, N-acetyl-D-galactosamine and N-acetyl-D-mannosamine units are frequently occurring in various biologically important oligosaccharides and their glycoconjugates. Due to their biological importance, a considerable effort has been devoted to the search for efficient methods of their synthesis.

In this project we focus on the development of novel and versatile methods and strategies for synthesis of oligosaccharides of hexosamine type particularly: (1) de novo synthesis of (1-4)-linked 2-amino-2-deoxy-cyclomannins and 2-amino-2-deoxy-cyclogalactins and (2) the development of stereoselective synthesis of 2-acetamido-analogs of β-mannopyranosides.

Polycationic transport systems for the construction of DNA vaccines and nucleic acid fragment analogs

The recent progress in gene therapy as well as DNA vaccination will significantly change the face of medicine during the first decade of the 21^st century, with substantial consequences for the way in which the pharmaceutical industry would adjust to these challenges. A major problem for the routine use of gene therapy and DNA vaccines in practice is the efficiency of the introduction of nucleic acids into cell nucleus, i.e., transfection process. Transfection of genes and nucleic acid agents into cell cytoplasma and nucleus can be regarded as a special problem in drug delivery. During the last decade, therefore, the great deal of attention was paied to the search for suitable non-viral vectors for nucleic acid delivery, because the use of viral vectors is limited by unpredictable immune response and safety.

Our research project is aimed on development of a new type of non-viral vectors. We focus on the following compounds: a) new type of spermine-based lipopolyamines, b) neoglycolipids derived from oligosaccharides of hexosamine type; c) multifunctional polycationic dendrimeric structures. These vectors can be also used for effective transport of analogs of nucleotides and oligonucleotides, including nucleotide antivirotics developed in Prof. A.Holý's laboratory.

Targeted modulation of NK-cells’ cytotoxicity by oligosaccharides and neoglycoconjugates

NK cells (natural killer cells) are intriguing targets of aimed modulation of innate immunity. Their activity can be modulated by signals transmitted by interaction of their surface receptors with appropriate natural ligands. A systematic study of the activation of lectin receptors of rat NKR-P family and human CD69 showed that complex natural oligosaccharide structures presented on the surface of carcinoma and infected cells exert binding affinity to these receptors. However, these ligands are not suitable for practical use as immunotherapeutics.

Our research program focuses on the search for their simplified and hence defined and better available mimetics and particularly on the design and synthesis of D-hexosamine type oligosaccharides and neoglycoconjugates as the optimal ligands for activating receptors of the human NK cells.