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Galectin-1 (hGal-1) is overexpressed by numerous cancer types and previously conducted studies confirmed that the β-galactoside-binding protein mediates various molecular interactions associated with tumor growth, spread and survival. Upon interaction with carbohydrate-based binding epitopes of glycan structures on human cell surfaces galectin-1 induces proliferative, angiogenetic and migratory signals and modulates negative T cell regulation which essentially helps the tumor to evade the immune response. These findings attributed galectin-1 a pivotal role in tumor physiology and strongly suggest the protein as target for diagnostic and therapeutic applications.
Within the scope of this work a strategy was elaborated for designing tailor-made galectin-1 ligands by functionalizing selected hydroxyl groups of the natural binding partner N-acetyllactosamine (LacNAc) that are not involved in the sophisticated interplay between the disaccharide and the protein. Synthetic modifications intended to introduce chemical groups i) to address a potential binding site adjacent to the carbohydrate recognition domain (CRD) with extended hGal-1-ligand interactions, ii) to implement a tracer isotope for diagnostic detection and iii) to install a linker unit for immobilization on microarrays.
Resulting structures were investigated regarding their targeting ability towards galectin-1 by cocrystallization experiments, SPR and ITC studies. Potent binders were further probed for their diagnostic potential to trace elevated galectin-1 levels in microarray experiments and for an application in positron emission tomography (PET).
The functional role of human gut microbiota has attracted substantial interest and recent research has uncovered various aspects of the interplay between the complex communities of microorganisms colonizing the intestine and their hosts’ health. The present review focuses on nutrition-derived bioactive metabolites produced by gut microbiota with potential beneficial effects upon human health. Thereby, the emphasis is on newly generated bacterial metabolites that are not concomitantly present at higher amounts in dietary sources and that have been previously detected in human blood samples. Since a multitude of different substances is generated by gut microbes primarily those metabolites which exert a more pronounced activity than their immediate precursor compound are discussed here. Specifically, the in vitro and in vivo nutridynamics as well as the nutrikinetics of equol, enterolactone / enterodiol, urolithins, 8-prenylnaringenin, 3,4-dihydroxyphenylacetic acid and 5-(3’,4’-dihydroxyphenyl)-g-valerolactone, the short-chain fatty acids butyrate, propionate and acetate, and indole-3-propionic acid are reviewed. Though the metabolites’ mechanism of action and the influence of health conditions on metabolite production are not always fully understood yet, there are many reasons to direct the attention to “gut health”. It could offer new options for preventing or treating a variety of disease states and nutrition-derived microbial products might inspire future drug development.