Chemoenzymatic synthesis of selective multivalent neo-glycoproteins for galectin-4 inhibition

• Applicant: Professor Dr. Lothar Elling
• Subject Area: Biological and Biomimetic Chemistry
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 471775640

We will prepare biocompatible neo-glycoproteins (NGP) for selective targeting of galectin-4 (Gal-4) and compare their affinity and selectivity to human Gal-1 and Gal-3. Selective galectin inhibition may be applied in the theranostics of galectin-related pathologies, e.g. heart diseases, cancerogenesis or immune disorders. The use of chemo-enzymatic platform technologies, namely the assembly of glycan epitopes and modified sugar building blocks in nature-like branches and the multivalent presentation of obtained branches on a protein carrier will yield neo-glycoproteins with tailored glycan avidity. We will prepare a library of poly-N-acetyllactosamine-based ABH blood group antigens and sulfated glycans to address specific binding of Gal-4 and by using click chemistry we will create glycan branches on di-O-propargyl and tetra-O-propargyl glucose building blocks and human serum albumin (HSA) neoglycoconjugates. The binding properties of Gal-4 with monovalent glycans and multivalent NGP will be studied using ELISA and SPR. The best candidates will be assayed for binding interaction with Gal-4-expressing cell lines.

• DFG Programme: Research Grants
• International Connection: Czech Republic
• Cooperation Partner: Professor Dr.-Ing. Vladimir Kren, Ph.D.