Abstract:
Glycans decorate all cells and are critical mediators of cellular processes through recognition by glycan-binding proteins (GBPs). While targeting glycan-protein interactions has great therapeutic potential, these interactions are challenging to study as they are generally transient and exhibit low binding affinities. Glycan-based photo-crosslinkable probes have enabled covalent capture and identification of unknown GBP receptors and glycoconjugate ligands. Here, we review recent progress in photo-crosslinking approaches targeting glycan-mediated interactions. We discuss two prominent emerging strategies: 1) development of photo-crosslinkable oligosaccharide ligands to identify GBP receptors; and 2) cell-surface glyco-engineering to identify glycoconjugate ligands of GBPs. Overall, photoaffinity labeling affords valuable insights into complex glycan-protein networks and is poised to help elucidate the glycan-protein interactome, providing novel targets for therapeutic intervention.
摘要:
聚糖装饰所有细胞,并且是通过聚糖结合蛋白(GBP)识别的细胞过程的关键介质。虽然靶向聚糖-蛋白质相互作用具有巨大的治疗潜力,这些相互作用是具有挑战性的研究,因为它们通常是短暂的,并表现出低的结合亲和力。基于聚糖的光交联探针已经能够共价捕获和鉴定未知的GBP受体和糖缀合物配体。这里,我们综述了针对聚糖介导的相互作用的光交联方法的最新进展。我们讨论了两种突出的新兴策略:1)开发可光交联的寡糖配体以鉴定GBP受体;2)细胞表面糖工程以鉴定GBP的糖缀合物配体。总的来说,光亲和标记为复杂的聚糖-蛋白质网络提供了有价值的见解,并准备帮助阐明聚糖-蛋白质相互作用组,为治疗干预提供新的靶点。