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

Authors: Tomáš Vašíček1, Vojtěch Spiwok2*, Jakub Červený1, Lucie Petrásková1, Ladislav Bumba1, Helena Pelantová1, Vladimír Křen1, Pavla Bojarová1*

  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/v2 (version v2, submitted on 22 January 2020)

How to cite this entry

Tomáš Vašíček, Vojtěch Spiwok, Jakub Červený, Lucie Petrásková, Ladislav Bumba, Helena Pelantová, Vladimír Křen, Pavla Bojarová, Regioselective 3-O-Substitution of Unprotected Thiodigalactosides: Direct Route to Galectin Inhibitors, Materials Cloud Archive (2020), doi: 10.24435/materialscloud:2020.0002/v2.

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.

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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.

License

Files and data are licensed under the terms of the following license: Creative Commons Attribution 4.0 International.

External references

Journal reference
T. Vašíček, V. Spiwok, J. Červený, L. Petrásková, L. Bumba, H. Pelantová, V. Křen, P. Bojarová, submitted (2020).

Keywords

galectin glycobiology molecular dynamics simulation

Version history

22 January 2020 [This version]

08 January 2020