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

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. A polymer that recognizes structural variations between different glycans could improve detection of breast and prostate cancer. Glycans attach to many kinds of biological molecules, making them essential information carriers between cells during processes such as tumor metastasis. Taolei Sun from Wuhan University of Technology and co-workers have now grafted olgiopeptide receptors onto polyethylenimine anchors for materials that capture potential glycan biomarkers from complex sample mixtures. Most glycan sensors only spot differences between the terminal saccharide groups that become attached to polymer surfaces. In contrast, the Chinese team's approach draws on hydrogen-bonding patterns found in nature to identify glycans with specific three-dimensional compositions and biomolecular connections. Immobilization of the smart polymer onto core-shell beads made from iron oxide and silicia allowed selected glycans to be easily separation by using magnetic fields. Sialylated complex-type N-linked glycans on cytomembrane are acknowledged as effective biomarkers for cancer diagnose. Owing to their complicated structures and low-abundance, developing glycan-targeted materials with high specificity is quite challenging. To resolve this problem, we reported a biomimetic design for dipeptide-based smart polymer, as well as its excellent performance in sialo-N-linked glycan recognition, adsorption, linkage isomers discrimination and high-efficiency capture from complex protein sample.