Neighboring substituent effects on ligand-protein halogen bond. Studies of m-chlorophenyl α-D-thiogalactoside ligands to Galectin-3

The galactoside-binding protein galectin-3 is commonly overexpressed by cancer cells and promotes cancer progression and metastasis. Over the past few years, evidence has emerged that galectin-3 is also overexpressed in several metabolic malfunction conditions such as diabetes, fibrosis, obesity and atherosclerosis and is involved in the regulation of the occurrence and development of these diseases. Recently, Galectin- 3 expression has also been shown to be associated with glycolysis and mitochondrial metabolism in tumors and promotes tumor metabolic reprogramming for their adaption to the micro-environment stress imposed by oxygen and nutrient deprivation. Hence the importance of finding powerful inhibitors. In this work, 6 different galectin-3 ligands with nM affinity have been synthesized, characterized and the interaction with the protein analyzed with Fluorescence Polarization (FP). Moreover, this thesis aims to show how the proximity of Electron Withdrawing Groups (EWG) or Hydrogen Bond Donor (HBD) groups to a Halogen (Cl) affect the strength of the Halogen Bond (XB) and, therefore, on the strength of the interaction with galectin-3.