Synthesis of mono- and multivalent inhibitors of tandem galectins

Galectins are a class of lectins (carbohydrate-binding proteins other than enzymes and antibodies) characterized by affinity to galactosides and sequence homology. So-called tandem galectins comprise two related but non-identical carbohydrate-binding domains (CRD) with partially different substrate specificities. Inhibition of tandem galectins by synthetic analogs of saccharides (glycomimetics) is of great importance in both fundamental research and drug development. The attachment of monovalent domain-specific inhibitors to suitable carriers will result in multivalent inhibitors that can inhibit both domains within the tandem galectin simultaneously and very effectively, if the right topology is achieved. The main goal of this PhD project is the synthesis and evaluation of glycomimetic inhibitors of individual domains and the verification of the hypothesis that an appropriate spatial arrangement of domain-specific inhibitors on a multivalent carrier can lead to high affinity inhibitors of tandem galectins due to a multivalent effect.

Reference:         Bertuzzi, S. et al. Front. Chem. 2020, 8 (593), DOI: 10.3389/fchem.2020.00593.

Required education and skills

• Master degree in chemistry.
• The willingness to learn and apply advanced methods of organic synthesis.

Co-supervisor: Prof. RNDR. Pavla Bojarová Ph.D.