Galectin-8 is a member of the family of lectins, proteins possessing special affinity for β-galactoside, which is detected both in normal and in tumor cells. It is involved in a wide range of cellular responses, such as cellular adhesion, growth arrest, apoptosis, pathogen recognition, autophagy and immunosuppression. Since galectin-8 expression can positively or negatively correlate with tumor progression or recurrence, measuring its level in the future could serve to detect cancer, as well as predict the prognosis of the disease and therapeutic efficacy.
Due to the involvement of galectins in many cellular processes and their role in the pathology of many diseases, the need for the discovery of their antagonists has developed. Despite the efforts of many researchers this area remains, in particular regarding galectin-8, rather unexplored, and the number of known antagonists is consequently rather limited.
Within this Master's thesis, we synthesized novel galectin-8 ligands by regioselective alkylation of methyl-β-D-galactopyranoside using organotin compounds. Their design was based on the structure of a recently reported ligand and the crystal structure of galectin-8. All synthesized compounds carry the methyl β-D-galactopyranoside fragment, but differ in the substituent at position 3. Synthetic procedures using dibutyltin dichloride were largely unsuccessful despite some modifications to the method, therefore another catalyst, dibutyltin oxide, was used instead. Although we encountered many problems during the synthesis, we successfully synthesized 7 end compounds. During the Master's thesis, we established and optimized the synthetic procedure, which can be used for further syntheses of 3-O-substituted methyl-β-galactopyranoside derivatives. Surprisingly, our compounds did not exhibit any binding to the protein, nevertheless they provided a better understanding of the structure-activity relationship of galectin-8 ligands.
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