Regioselective 3-O-Substitution of Unprotected Thiogalactosides: Route to Specific Galectin Inhibitors Introduction: 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. Files: QM/benzyl/benzyl.com Quantum-chemical optimization of a model complex for 6 with Arg144 - input file QM/benzyl/benzyl.com.out Quantum-chemical optimization of a model complex for 6 with Arg144 - output file QM/benzyl/mp2/benzyl.com Quantum-chemical interaction energy of a model complex for 6 with Arg144 - input file QM/benzyl/mp2/benzyl.com.out Quantum-chemical interaction energy of a model complex for 6 with Arg144 - output file QM/Brnaphtyl/Brnaphtyl.com Quantum-chemical optimization of a model complex for 13 with Arg144 - input file QM/Brnaphtyl/Brnaphtyl.com.out Quantum-chemical optimization of a model complex for 13 with Arg144 - output file QM/Brnaphtyl/mp2/Brnaphtyl.com Quantum-chemical interaction energy of a model complex for 13 with Arg144 - input file QM/Brnaphtyl/mp2/Brnaphtyl.com.out Quantum-chemical interaction energy of a model complex for 13 with Arg144 - output file QM/coumaryl/coumaryl.com Quantum-chemical optimization of a model complex for 5 with Arg144 - input file QM/coumaryl/coumaryl.com.out Quantum-chemical optimization of a model complex for 5 with Arg144 - output file QM/coumaryl/mp2/coumaryl.com Quantum-chemical interaction energy of a model complex for 5 with Arg144 - input file QM/coumaryl/mp2/coumaryl.com.out Quantum-chemical interaction energy of a model complex for 5 with Arg144 - output file QM/naphtyl/naphtyl.com Quantum-chemical optimization of a model complex for 12 with Arg144 - input file QM/naphtyl/naphtyl.com.out Quantum-chemical optimization of a model complex for 12 with Arg144 - output file QM/naphtyl/mp2/naphtyl.com Quantum-chemical interaction energy of a model complex for 12 with Arg144 - input file QM/naphtyl/mp2/naphtyl.com.out Quantum-chemical interaction energy of a model complex for 12 with Arg144 - output file QM/tdg/tdg.com Quantum-chemical optimization of a model complex for 1 with Arg144 - input file QM/tdg/tdg.com.out Quantum-chemical optimization of a model complex for 1 with Arg144 - output file QM/tdg/mp2/tdg.com Quantum-chemical interaction energy of a model complex for 1 with Arg144 - input file QM/tdg/mp2/tdg.com.out Quantum-chemical interaction energy of a model complex for 1 with Arg144 - output file MD/gal1/benzyl/afternvt5.gro Molecular dynamics of a complex of galectin 1 with 6 - initial structure MD/gal1/benzyl/md1_10fit100.xtc Molecular dynamics of a complex of galectin 1 with 6 - 100 ns trajectory MD/gal1/benzyl/rmsd.xvg Molecular dynamics of a complex of galectin 1 with 6 - RMSD profile MD/gal1/benzyl/benzyl_gal1.mpg Molecular dynamics of a complex of galectin 1 with 6 - movie MD/gal1/naphtyl/afternvt5.gro Molecular dynamics of a complex of galectin 1 with 12 - initial structure MD/gal1/naphtyl/md1_10fit100.xtc Molecular dynamics of a complex of galectin 1 with 12 - 100 ns trajectory MD/gal1/naphtyl/rmsd.xvg Molecular dynamics of a complex of galectin 1 with 12 - RMSD profile MD/gal1/naphtyl/naphtyl_gal1.mpg Molecular dynamics of a complex of galectin 1 with 12 - movie MD/gal1/tdg/afternvt5.gro Molecular dynamics of a complex of galectin 1 with 1 - initial structure MD/gal1/tdg/md1_10fit100.xtc Molecular dynamics of a complex of galectin 1 with 1 - 100 ns trajectory MD/gal1/tdg/rmsd.xvg Molecular dynamics of a complex of galectin 1 with 1 - RMSD profile MD/gal1/tdg/tdg_gal1.mpg Molecular dynamics of a complex of galectin 1 with 1 - movie MD/gal3/benzyl1/afternvt5.gro Molecular dynamics of a complex of galectin 3 with 6 - binding mode A - initial structure MD/gal3/benzyl1/md1_10fit100.xtc Molecular dynamics of a complex of galectin 3 with 6 - binding mode A - 100 ns trajectory MD/gal3/benzyl1/rmsd.xvg Molecular dynamics of a complex of galectin 3 with 6 - binding mode A - RMSD profile MD/gal3/benzyl1/benzy_gal3_mode1.mpg Molecular dynamics of a complex of galectin 3 with 6 - binding mode A - movie MD/gal3/benzyl2/afternvt5.gro Molecular dynamics of a complex of galectin 3 with 6 - binding mode B - initial structure MD/gal3/benzyl2/md1_10fit100.xtc Molecular dynamics of a complex of galectin 3 with 6 - binding mode B - 100 ns trajectory MD/gal3/benzyl2/rmsd.xvg Molecular dynamics of a complex of galectin 3 with 6 - binding mode B - RMSD profile MD/gal3/benzyl2/benzyl_gal3_mode2.mpg Molecular dynamics of a complex of galectin 3 with 6 - binding mode B - movie MD/gal3/brnaphtyl1/afternvt5.gro Molecular dynamics of a complex of galectin 3 with 13 - binding mode A - initial structure MD/gal3/brnaphtyl1/md1_10fit100.xtc Molecular dynamics of a complex of galectin 3 with 13 - binding mode A - 100 ns trajectory MD/gal3/brnaphtyl1/rmsd.xvg Molecular dynamics of a complex of galectin 3 with 13 - binding mode A - RMSD profile MD/gal3/brnaphtyl1/Brnaphtyl_gal3_mode1.mpg Molecular dynamics of a complex of galectin 3 with 13 - binding mode A - movie MD/gal3/brnaphtyl2/afternvt5.gro Molecular dynamics of a complex of galectin 3 with 13 - binding mode B - initial structure MD/gal3/brnaphtyl2/md1_10fit100.xtc Molecular dynamics of a complex of galectin 3 with 13 - binding mode B - 100 ns trajectory MD/gal3/brnaphtyl2/rmsd.xvg Molecular dynamics of a complex of galectin 3 with 13 - binding mode B - RMSD profile MD/gal3/brnaphtyl2/Brnaphtyl_gal3_mode2.mpg Molecular dynamics of a complex of galectin 3 with 13 - binding mode B - movie MD/gal3/coumaryl1/afternvt5.gro Molecular dynamics of a complex of galectin 3 with 5 - binding mode A - initial structure MD/gal3/coumaryl1/md1_10fit100.xtc Molecular dynamics of a complex of galectin 3 with 5 - binding mode A - 100 ns trajectory MD/gal3/coumaryl1/rmsd.xvg Molecular dynamics of a complex of galectin 3 with 5 - binding mode A - RMSD profile MD/gal3/coumaryl1/coumaryl_gal3_model1.mpg Molecular dynamics of a complex of galectin 3 with 5 - binding mode A - movie MD/gal3/coumaryl2/afternvt5.gro Molecular dynamics of a complex of galectin 3 with 5 - binding mode B - initial structure MD/gal3/coumaryl2/md1_10fit100.xtc Molecular dynamics of a complex of galectin 3 with 5 - binding mode B - 100 ns trajectory MD/gal3/coumaryl2/rmsd.xvg Molecular dynamics of a complex of galectin 3 with 5 - binding mode B - RMSD profile MD/gal3/coumaryl2/coumaryl_gal3_model2.mpg Molecular dynamics of a complex of galectin 3 with 5 - binding mode B - movie MD/gal3/naphtyl1/afternvt5.gro Molecular dynamics of a complex of galectin 3 with 12 - binding mode A - initial structure MD/gal3/naphtyl1/md1_10fit100.xtc Molecular dynamics of a complex of galectin 3 with 12 - binding mode A - 100 ns trajectory MD/gal3/naphtyl1/rmsd.xvg Molecular dynamics of a complex of galectin 3 with 12 - binding mode A - RMSD profile MD/gal3/naphtyl1/naphtyl_gal3_mode1.mpg Molecular dynamics of a complex of galectin 3 with 12 - binding mode A - movie MD/gal3/naphtyl2/afternvt5.gro Molecular dynamics of a complex of galectin 3 with 12 - binding mode B - initial structure MD/gal3/naphtyl2/md1_10fit100.xtc Molecular dynamics of a complex of galectin 3 with 12 - binding mode B - 100 ns trajectory MD/gal3/naphtyl2/rmsd.xvg Molecular dynamics of a complex of galectin 3 with 12 - binding mode B - RMSD profile MD/gal3/naphtyl2/naphtyl_gal3_mode2.mpg Molecular dynamics of a complex of galectin 3 with 12 - binding mode B - movie MD/gal3/tdg/afternvt5.gro Molecular dynamics of a complex of galectin 3 with 1 - initial structure MD/gal3/tdg/md1_10fit100.xtc Molecular dynamics of a complex of galectin 3 with 1 - 100 ns trajectory MD/gal3/tdg/rmsd.xvg Molecular dynamics of a complex of galectin 3 with 1 - RMSD profile MD/gal3/tdg/tdg_gal3.mpg Molecular dynamics of a complex of galectin 3 with 1 - movie