Regioselective 3-O-Substitution of Unprotected Thiodigalactosides: Direct Route to Galectin Inhibitors.

Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 9513783 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-3765 (Electronic) Linking ISSN: 09476539 NLM ISO Abbreviation: Chemistry Subsets: MEDLINE

Original Publication: Weinheim, Germany : Wiley-VCH

Carbohydrates/*chemistry ; Galectin 1/*chemistry ; Galectin 3/*chemistry ; Galectins/*chemistry ; Thiogalactosides/*chemistry; Blood Proteins ; Galactose ; Galectin 1/metabolism ; Galectin 3/metabolism ; Galectins/metabolism ; Humans ; Models, Molecular

The synthesis of tailored bioactive carbohydrates usually comprises challenging (de)protection steps, which lowers synthetic yields and increases time demands. We present here a regioselective single-step introduction of benzylic substituents at 3-hydroxy groups of β-d-galactopyranosyl-(1→1)-thio-β-d-galactopyranoside (TDG) employing dibutyltin oxide in good yields. These glycomimetics act as inhibitors of galectins-human lectins, which are biomedically attractive targets for therapeutic inhibition in, for example, cancerogenesis. The affinity of the prepared glycomimetics to galectin-1 and galectin-3 was studied in enzyme-linked immunosorbent (ELISA)-type assays and their potential to inhibit galectin binding on the cell surface was shown. We used our original in vivo biotinylated galectin constructs for easy detection by flow cytometry. The results of the biological experiments were compared with data from molecular modeling with both galectins. The present work reveals a facile and elegant synthetic route for the preparation of TDG-derived glycomimetics that exhibit differing selectivity and affinity to galectins depending on the choice of 3-O-substitution.
(© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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LTC18038 Ministerstvo Školství, Mládeže a Tělovýchovy; LTC19038 Ministerstvo Školství, Mládeže a Tělovýchovy; LM2018133 Ministerstvo Školství, Mládeže a Tělovýchovy; LM2018140 Ministerstvo Školství, Mládeže a Tělovýchovy; LM2015047 Ministerstvo Školství, Mládeže a Tělovýchovy

Keywords: carbohydrates; glycomimetics; glycosides; inhibitors; molecular modeling

0 (Blood Proteins)
0 (Carbohydrates)
0 (Galectin 1)
0 (Galectin 3)
0 (Galectins)
0 (LGALS3 protein, human)
0 (Thiogalactosides)
80441-61-8 (thiodigalactoside)
X2RN3Q8DNE (Galactose)

Date Created: 20200506 Date Completed: 20201026 Latest Revision: 20211204

20240829

10.1002/chem.202002084

32368810