Department of Chemistry, Umeå University, 90187, Umeå, Sweden.
Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., 44227, Dortmund, Germany.
Angew Chem Int Ed Engl. 2023 Aug 7;62(32):e202302437. doi: 10.1002/anie.202302437. Epub 2023 May 17.
Mucin glycoproteins are essential components of the mucosal barrier, which protects the host from pathogens. Throughout evolution, bacteria have developed strategies to modulate and penetrate this barrier, and cause virulence by interacting with mucin O-glycans at the epithelial cell-surface. O-fucosylated glycan epitopes on mucins are key ligands of many bacterial lectins. Here, a chemoenzymatic synthesis strategy is described to prepare a library of fucosylated mucin core glycopeptides to enable studies of mucin-interacting and fucose-binding bacterial lectins. Glycan cores with biologically important Lewis and H-antigens were prepared decorating the peptide backbone at different sites and densities. The fucosylated mucin glycopeptides were applied in microarray binding studies to explore the importance of glycan core and peptide backbone presentation of these antigens in binding interactions with the P. aeruginosa lectin LecB and the C. difficile toxin A.
粘蛋白糖蛋白是黏膜屏障的重要组成部分，可保护宿主免受病原体侵害。在整个进化过程中，细菌已经开发出了各种策略来调节和穿透这一屏障，并通过与上皮细胞表面的粘蛋白 O-聚糖相互作用而产生毒力。粘蛋白上的 O-岩藻糖基化聚糖表位是许多细菌凝集素的关键配体。本文描述了一种化学酶合成策略，用于制备岩藻糖基化粘蛋白核心糖肽文库，以研究与粘蛋白相互作用和结合岩藻糖的细菌凝集素。通过在不同位置和密度处修饰肽骨架，制备了具有生物学重要的 Lewis 和 H 抗原的糖基核心。将岩藻糖基化粘蛋白糖肽应用于微阵列结合研究中，以探讨这些抗原的糖基核心和肽骨架在与铜绿假单胞菌凝集素 LecB 和艰难梭菌毒素 A 结合相互作用中的呈现方式的重要性。
