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

点击翻译按钮获取中文摘要

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.