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

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{
  "revision": 3, 
  "id": "290", 
  "created": "2020-05-12T13:53:35.155343+00:00", 
  "metadata": {
    "doi": "10.24435/materialscloud:2020.0002/v1", 
    "status": "published", 
    "title": "Regioselective 3-O-Substitution of Unprotected Thiodigalactosides: Route to Specific Galectin Inhibitors", 
    "mcid": "2020.0002/v1", 
    "license_addendum": "", 
    "_files": [
      {
        "description": "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.\r\nMolecular 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.", 
        "key": "galectin.zip", 
        "size": 159775376, 
        "checksum": "md5:fa1a4f03de19bf5c58db06a30d28ad14"
      }, 
      {
        "description": "README file with list and description of files.", 
        "key": "README.txt", 
        "size": 9674, 
        "checksum": "md5:14ae449dc2a6690848d3d4bb52ed588f"
      }
    ], 
    "owner": 299, 
    "_oai": {
      "id": "oai:materialscloud.org:290"
    }, 
    "keywords": [
      "molecular dynamics simulation", 
      "glycobiology", 
      "galectin"
    ], 
    "conceptrecid": "289", 
    "is_last": false, 
    "references": [
      {
        "type": "Journal reference", 
        "doi": "", 
        "url": "", 
        "comment": "", 
        "citation": "T. Va\u0161\u00ed\u010dek, V. Spiwok, J. \u010cerven\u00fd, L. Petr\u00e1skov\u00e1, L. Bumba, H. Pelantov\u00e1, V. K\u0159en, P. Bojarov\u00e1, submitted (2020)."
      }
    ], 
    "publication_date": "Jan 08, 2020, 00:00:00", 
    "license": "Creative Commons Attribution 4.0 International", 
    "id": "290", 
    "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.\r\nIn 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.\r\nMolecular 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.", 
    "version": 1, 
    "contributors": [
      {
        "affiliations": [
          "Institute of Microbiology, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"
        ], 
        "familyname": "Va\u0161\u00ed\u010dek", 
        "givennames": "Tom\u00e1\u0161"
      }, 
      {
        "email": "spiwokv@vscht.cz", 
        "affiliations": [
          "Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, Czech Republic"
        ], 
        "familyname": "Spiwok", 
        "givennames": "Vojt\u011bch"
      }, 
      {
        "affiliations": [
          "Institute of Microbiology, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"
        ], 
        "familyname": "\u010cerven\u00fd", 
        "givennames": "Jakub"
      }, 
      {
        "affiliations": [
          "Institute of Microbiology, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"
        ], 
        "familyname": "Petr\u00e1skov\u00e1", 
        "givennames": "Lucie"
      }, 
      {
        "affiliations": [
          "Institute of Microbiology, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"
        ], 
        "familyname": "Bumba", 
        "givennames": "Ladislav"
      }, 
      {
        "affiliations": [
          "Institute of Microbiology, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"
        ], 
        "familyname": "Pelantov\u00e1", 
        "givennames": "Helena"
      }, 
      {
        "affiliations": [
          "Institute of Microbiology, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"
        ], 
        "familyname": "K\u0159en", 
        "givennames": "Vladim\u00edr"
      }, 
      {
        "email": "bojarova@biomed.cas.cz", 
        "affiliations": [
          "Institute of Microbiology, Academy of Sciences of the Czech Republic, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"
        ], 
        "familyname": "Bojarov\u00e1", 
        "givennames": "Pavla"
      }
    ], 
    "edited_by": 100
  }, 
  "updated": "2021-01-26T14:45:30.124651+00:00"
}