Tomáš Vašíček¹, Vojtěch Spiwok^2*, Jakub Červený¹, Lucie Petrásková¹, Ladislav Bumba¹, David Vrbata¹, Helena Pelantová¹, Vladimír Křen¹, Pavla Bojarová^1*

1 Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 14220 Prague 4, Czech Republic

2 Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Czech Republic

* Corresponding authors emails: spiwokv@vscht.cz, bojarova@biomed.cas.cz

DOI10.24435/materialscloud:2020.0002/v3 [version v3]

Publication date: May 05, 2020

How to cite this record

Tomáš Vašíček, Vojtěch Spiwok, Jakub Červený, Lucie Petrásková, Ladislav Bumba, David Vrbata, Helena Pelantová, Vladimír Křen, Pavla Bojarová, Regioselective 3-O-Substitution of Unprotected Thiodigalactosides: Direct Route to Galectin Inhibitors, Materials Cloud Archive 2020.0002/v3 (2020), https://doi.org/10.24435/materialscloud:2020.0002/v3

Description

Regioselective derivatization of oligosaccharides is a challenging issue in carbohydrate chemistry. A commonly required series of (de)protection steps substantially lowers synthetic yields and increases time demands. We present here a regioselective one-step introduction of benzylic substituents at 3-hydroxy moieties of beta-D-galactopyranosyl-(1<->1)-thio-beta-D-galactopyranoside (TDG) employing tin butyl oxide in fair isolated yields. These glycomimetics act as inhibitors of galectins - human lectins, which are biomedically attractive targets for therapeutic inhibition. The affinity of prepared glycomimetics to recombinant galectin-1 and galectin-3 was studied in ELISA-type assay and their inhibitory potential was also demonstrated on the surface of a model HEK293 cell line. The results of biological experiments were correlated with data from molecular modelling with both galectins. The present work reveals a facile and elegant synthetic route for the preparation of glycomimetics that exhibit differing selectivity and affinity to various galectins depending on the choice of 3-O-substitution. In order to rationalize structure-activity relationships of tested ligands we carried out a series of molecular dynamics simulations and quantum chemical calculations. We present input and output files for quantum chemical geometry optimizations and calculations of interactions energies. These calculations were carried out in Gaussian 09 package. These results can be visualized using Molden, Molekel or other programs. Molecular dynamics simulations were carried out using Gromacs 5.1.3 package. Initial structures of production simulations and trajectories (without water) are presented. The results can be visualized by VMD or other structure visualization packages with a support for trajectory input.

Materials Cloud sections using this data

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File name	Size	Description
galectin.zip MD5md5:bf46ad82210ee96e327414481a53a2c1	152.4 MiB	In order to rationalize structure-activity relationships of tested ligands we carried out a series of molecular dynamics simulations and quantum chemical calculations. We present input and output files for quantum chemical geometry optimizations and calculations of interactions energies. These calculations were carried out in Gaussian 09 package. These results can be visualized using Molden, Molekel or other programs. Molecular dynamics simulations were carried out using Gromacs 5.1.3 package. Initial structures of production simulations and trajectories (without water) are presented. The results can be visualized by VMD or other structure visualization packages with a support for trajectory input.
README.txt MD5md5:f8a169b57b257220d17fc42770a1494a	9.4 KiB	README file with list and description of files.

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Keywords

glycobiology molecular dynamics simulation galectin