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. The so-called tandem galectins comprise two related but non-identical carbohydrate-binding domains (CRD) with a partially different substrate specificity. The inhibition of tandem galectins by synthetic analogs of saccharides (glycomimetics) is of principal significance in fundamental research as well as in drug development. Attachment of monovalent domain-specific inhibitors to suitable carriers will give rise to 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 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.

Required education and skills

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

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