A biomimetic design for a sialylated, glycan-specific smart polymer

Abstract

Increasing evidence has indicated that glycans and their interactions with glycan-specific binding proteins have crucial roles in most physiological processes. One emerging topic in biomaterials is the construction of smart materials capable of recognizing and responding to these valuable glycans. However, because of the complicated compositions and structures as well as the low abundances and microheterogeneity of glycans, developing glycan-responsive materials with a high sensitivity and specificity is a long-term, challenging goal. Here, we report a biomimetic polymer capable of capturing and discriminating sialo-complex-type glycans with the core Neu5Ac-Gal-GlcNAc-Man sequence, which is one of the most effective biomarkers for cancer detection. As an optimized dipeptide, L-Asp-L-Phe has a strong but differential binding affinity for N-acetyl-neuraminic acid (Neu5Ac), N-acetyl-glucosamine (GlcNAc), galactose (Gal), and mannose (Man), which are the core construction units of sialylated glycans. In addition, the L-Asp-L-Phe-grafted polyethyleneimine film displays remarkable adsorption behavior for the model sialylated glycans and can discriminate their linkage isomers, which is accompanied by significant changes in the surface morphology and stiffness. These features facilitate the highly selective capture of sialylated glycopeptides from complex protein samples using PEI-g-L-Asp-L-Phe-modified mSiO2@SiO2@Fe3O4 core-shell microspheres. The mechanism analysis demonstrates that the favorable polymeric spatial structures and multiple synergetic hydrogen-bonding interactions among the dipeptides and glycan are the main driving forces, indicating a clear direction for designing glycan-specific biomaterials.