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Detailed Investigation of Human Galectins -1 and -3 by employing selectively deoxyfluorinated N-acetyllactosamines
Kurfiřt, Martin
This work is focused on a detailed investigation of supramolecular recognition events between human galectins -1 and -3 and monodeoxyfluorinated N-acetyllactosamine probes, which were previously prepared in our laboratory. The recognition was studied using a combination of X-ray crystallography, isothermal titration calorimetry and several advanced NMR techniques, such as 19F T2-filter, 1H–1H STD, 1H–15N CSP or 19F EXSY. These techniques provided insight into the thermodynamics and kinetics of recognition and enabled us to uncover of subtle differences between both investigated galectins. Such differences could be potentially exploited in the selective targeting of individual galectins with important implications for the galectins-focused\npharmaceutic industry.
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Deoxyfluorinated N-acetyllactosamines as carbohydrate-based probes for human galectins
Kurfiřt, Martin
This work is focused on a detailed NMR investigation of human galectins via a complete series of mono-deoxyfluorinated Nacetyllactosamine probes 1–6, which were prepared previously in our laboratory.3 Advanced 19F NMR T2-filter technique enabled the identification of hydroxyl groups essential for the interaction with varioushGals, and permitted to compare hGals in terms of the importance of these key hydroxyl groups in the recognition events. Furthermore, the library was also investigated by various NMR techniques such as 19F EXSY, STD and 15N CSP to reveal the molecular origin of recognition events.\n
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Deoxyfluorinated N-acetyllactosamines as Tailored Carbohydrate-based Probes for Human Galectins.
Kurfiřt, Martin
this work, I prepared a complete series of mono‑deoxyfluorinated N-acetyllactosamine analogues 1-6. The synthesis of each analogue\nrequired approximately 15 synthetic steps, including deoxyfluorination of monosaccharide precursors, chemical glycosylation and\ndeprotection. Their binding affinities to the two most explored human galectin-1 and -3 were determined by ELISA and 19F NMR T2-filter\ntechniques, which enabled the identification of hydroxyl groups, crucial in the non-covalent recognition by galectins. This binding study\nalso permitted to compare both tested galectins in terms of their substrate specificity, revealing subtle differences, which could be utilized\nin the development of selective galectin inhibitors. Furthermore, the series is also a perfect tool to study the molecular origin of recognition\nevents via epitope-mapping 19F NMR techniques.
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