Deoxyfluorination as a Promising Synthetic Approach to Selective Carbohydrate-based Galectin Inhibitors.

0550047 - ÚCHP 2022 CZ eng A - Abstrakt
Kurfiřt, Martin - Dračínský, Martin - Bojarová, Pavla - Valverde, P. - Cañada, J. - Karban, Jindřich
Deoxyfluorination as a Promising Synthetic Approach to Selective Carbohydrate-based Galectin Inhibitors.
Book of abstracts. 2021.
[Conference Advances in Organic, Bioorganic and Pharmaceutical Chemistry "LIBLICE 2021" /55./. 03.11.2021-06.11.2021, Špindlerův Mlýn]
Grant CEP: GA MŠMT(CZ) LTC20052; GA MŠMT(CZ) LTC20072; GA ČR(CZ) GA20-01472S
Institucionální podpora: RVO:67985858 ; RVO:61388963 ; RVO:61388971
Klíčová slova: galectins * NMR spectroscopy * fluorinated carbohydrates
Obor OECD: Organic chemistry; Organic chemistry (MBU-M); Organic chemistry (UOCHB-X)

Human galectins (hGals) are carbohydrate-binding proteins playing key roles in a plethora of physiological processes. They are able to modulate immune responses or neoplastic transformation processes via molecular recognition of galactoside-containing glycans.1 Therefore, the development of their selective inhibitors has become a focus of pharmaceutical research. However, the preparation of inhibitors targeting individual hGals remains challenging as 12 hGals featuring similar substrate specificities have been identified. A deeper understanding of differences between individual hGals could facilitate the development of galectin inhibitors, and deoxyfluorinated carbohydrates are established tools capable of providing such valuable information.2 In this work, a complete series of mono-deoxyfluorinated N-acetyllactosamine analogues have been prepared. The synthesis of each analogue required approximately 15 synthetic steps, including deoxyfluorination of monosaccharide precursors and chemical glycosylation.3 Their binding affinities to hGals were determined by ELISA assay and 19F NMR T2-filter techniques which enabled the identification of hydroxyl groups essential for the interaction with various hGals 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.
Trvalý link: http://hdl.handle.net/11104/0325899