Glycoclusters as tool for inhibiton of lectin mediated bacterial adhesion
| Název česky | Glykoklustry jako nástroj pro inhibici bakteriální adheze zprostředkované lektiny |
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| Autoři | |
| Rok publikování | 2018 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Lectins are carbohydrate recognizing proteins involved in intercellular interactions [1]. Amongst various biological processes that lectins play a crucial role in, we focus on the lectin mediated bacterial adhesion to the host tissues. Pathogenic bacteria use lectins to read the glyco-code presented on the host cell surface and adhere to the tissue, which is the initial step of bacterial infection development [1]. Several lectins with different sugar specificity were identified in Burkholderia cenocepacia [2] and Pseudomonas aeruginosa [3], opportunistic pathogens causing nosocomial infections in a cystic fibrosis patient. Our goal is to find a molecule with a high affinity towards lectin to competitively inhibit the bacterial adhesion to the host tissue and stop the infection at its very beginning. Glycomimetics with calixarene scaffold core were prepared. These cores were modified with a different number of saccharides positioned on linkers with variable length. According to the specificity of targeted lectin, L-fucose, D-galactose or D-mannose monosaccharide was used. Hemagglutination with purified lectins was used to evaluate lectin activity, as a classical, simple and inexpensive method. As lectins are multivalent proteins, they can bind to cells with suitable saccharides on their surfaces, cross-link the cells and form clusters easily visible in the microscope. Multivalent glycomimetics were used to inhibit lectin hemagglutination activity and the compound potency was compared with monosaccharide inhibitor. The capability of glycomimetics to function on the cellular level was tested in bacterial cross-linking studies. We were able to discover promising compounds capable to inhibit lectin activity in solution and with proven interaction with the bacterial cell wall. These compounds should be further tested, as they could be potential candidates for antiadhesive therapy development. |
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