0598971 - ÚCHP 2025 SK eng A - Abstrakt
Karban, Jindřich - Hamala, Vojtěch - Kurfiřt, Martin - Kozák, Jaroslav - Ostatná, Veronika
FERROCENE-MODIFIED DISACCHARIDES AS GALECTIN INHIBITORS.
Book of abstracts. Bratislava: Institute of Chemistry, Slovak Academy of Science, 2024. s. 57, č. článku FP4. ISBN 978-80-971665-7-1. ISSN 1339-7036.
[Bratislava Symposium on Sacharides /16./. 23.09.2024-27.09.2024, Smolenice Castle]
Grant CEP: GA ČR(CZ) GA23-06115S
Institucionální podpora: RVO:67985858 ; RVO:61388963 ; RVO:68081707
Klíčová slova: galectins * ferrocenes * inhibitors * thiodigalactosides
Obor OECD: Organic chemistry; Organic chemistry (UOCHB-X); Organic chemistry (BFU-R)

Galectins are β-galactoside-binding lectins widely distributed in animals and fungi. Approximately 16 galectins have been described in mammals and their dysregulation is associated with pathological conditions such as fibrosis, inflammation and cancer. The availability of selective galectin inhibitors is important for dissecting the biological functions of galectins. Moreover, pharmacological inhibition of human galectins is investigated as a potential therapeutic approach. One of the most potent galectin inhibitors, named TD139, is based on the thiodigalactoside scaffold with a 3-fluorophenyl ring attached to the 3- and 3′-positions via a triazole linker. TD139 is a potent single-digit nanomolar inhibitor of human galectin-3 (hgal-3) and approximately an order of magnitude weaker inhibitor of human galectin-1 (hgal-1) [1][2]. Substituting ferrocene for the fluorophenyl ring resulted in ferrocene-modified thiodigalactoside 1. The binding affinity of disaccharide 1 toward hgal-1 and -3 was determined using fluorescence polarization, isothermal titration calorimetry and intrinsic fluorescence of tryptophan residues. Ferrocene-modified disaccharide 1 exhibited significantly lower binding affinity for hgal-3 than TD139, but approximately 7-fold higher binding affinity for hgal-1 relative to hgal-3, making disaccharide 1 one of the most selective and potent hgal-1 inhibitors reported to date.
Trvalý link: https://hdl.handle.net/11104/0356545