engleski

Glycobiology of disease: basis for design and development of new drugs

Molecular recognition between oligosaccharides of glycoconjugates (GC) and their physiological receptors - lectins is a central event in a variety of biological phenomena and the first step in numerous processes based on cell-cell and cell-cellular matrix interactions. Interactions between lectins and glycoproteins, glycolipids or proteoglycans are involved in physiological processes such as fertilization, embryogenesis, cell migration, organ formation, immune defense and microbial infection. Many diseases and stress conditions are associated with modified carbohydrate parts of GC resulting in altered biological functions. In the same time activity and/or expression of lectins could be changed. Many pathogens use lectins to attach to host cells and initiate diseases. THe first line of defense are decoy oligosaccharides in mucose layers and in body fluids that bind to the microbe's lectins and prevent bacterial attachment and separate bacteria already attached. Today, one of the biggest challenges for pharmaceutical industry is synthesis of oligosaccharide analogs (OA), which could be alternatives to, or supplements to antibiotics. The other potent applications of OA could be prevention of metastasis formation: some tumors express specific lectins crucial for adhesion and invasion. Tumor cells also express modified GC so design of specific carbohydrate-binding molecules (CBM) could be also of a great interest. Furthermore, it opens possibilities to create tissue or cell specific drugs: designing microcapsules coated with specific CBM or OA could provide approach to highly specific targeting of drugs. Selectins, lectins expressed on leukocytes and endothelial cells, are also possible target for application of OA because blocking of specific leukocyte attachment to blood vessel endothelium could prevent extravasation and in that way supress inflammation. Glycobiology is new, very potent and rapidly developing science that provides data about many biological phenomena, thus opening a wide basis for design and development of new drugs.

glycobiology; disease; drug design

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