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

我们将制备可选择性靶向半乳糖凝集素-4 （Gal-4）的生物相容性新糖蛋白（NGP），并比较其与人类Gal-1和Gal-3的亲和力和选择性。选择性半乳糖凝集素抑制可应用于半乳糖凝集素相关病理的治疗，如心脏病、癌症发生或免疫紊乱。利用化学酶平台技术，即在类似自然的分支中组装聚糖表位和修饰的糖构建块，以及在蛋白质载体上多价呈现所获得的分支，将产生具有定制聚糖贪婪度的新糖蛋白。我们将准备一个基于聚n -乙酰乳胺的ABH血型抗原和巯基聚糖库，以解决Gal-4的特异性结合，并通过点击化学，我们将在二o -丙炔和四o -丙炔葡萄糖构建块和人血清白蛋白（HSA）新糖缀合物上创建聚糖分支。利用ELISA和SPR研究Gal-4与单价聚糖和多价NGP的结合特性。将对最佳候选蛋白与表达gal -4的细胞系的结合相互作用进行检测。

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.