Expedient Assembly of Multiantennary <i>N</i>-Glycans from Common <i>N</i>-Glycan Cores with Orthogonal Protection for the Profiling of Glycan-Binding Proteins
Ruofan Li, Pengxi Chen, Yi‐Fang Zeng, Tzu‐Hao Tseng, Veeranjaneyulu Gannedi, Larissa B. Krasnova, Chi‐Huey Wong
Abstract
High Resolution Image Download MS PowerPoint Slide Complex-type N -glycans are structurally diverse molecules, responsible for many biological processes, yet the specific sequences of N -glycans involved in biological recognition remain largely unknown. Despite the recent development of many efficient chemoenzymatic approaches, it is still lacking a general approach to produce structurally diverse complex-type N -glycans. Here, we designed two common precursors equipped with orthogonal protecting groups for antennary differentiation and selective glycan elongation. The N -acetyllactosamine (LacNAc) repeat modules were synthesized separately based on iterative Au(I) promoted glycosylation and programmable one-pot strategy and were incorporated into the N -glycan core structure in a site-specific manner. The final removal of benzyl groups was cleanly achieved using pressurized flow chemistry. A total of 51 N -glycans were assembled and presented as an array to study the binding specificity toward a panel of influenza hemagglutinins and other lectins. The established method allows a rapid and previously infeasible synthesis of asymmetric bi- and triantennary N -glycans, especially with the LacNAc repeats residing at a specific arm, bringing in new opportunities to study carbohydrate–receptor interactions.