Molecularly imprinted materials for glycan recognition and processing

Abstract

Carbohydrates are the most abundant organic molecules on Earth and glycosylation is the most common posttranslational modification of proteins. Glycans are involved in a plethora of biological processes including cell adhesion, bacterial and viral infection, inflammation, and cancer development. Coincidently, glycosides were some of the earliest molecules imprinted and have been instrumental in the development of covalent molecular imprinting technology. This perspective illustrates recently developed molecularly imprinted materials for glycan binding and processing. Novel imprinting techniques and postmodification led to development of synthetic glycan-binding materials capable of competing with natural lectins in affinity and artificial glycosidases for selective hydrolysis of complex glycans. These materials are expected to significantly advance glycochemistry, glycobiology, and related areas such as biomass conversion.

Fig. 1. Representative biological glycans, with glycan determinants shown in different-colored ovals in 1. The hydroxyls of OVA glycan 2 that can potentially form boronate esters are colored red.

Fig. 2. (a) Crystal structure of BOA (PDB ID: 4gk9), with the peptide chain colored from blue (N-terminus) through the rainbow spectrum to red (C-terminus). Four molecules of 3α,6α-mannopentaose are bound by the lectin and the glycans bound close to the N- and C-terminus are highlighted with sphere models. (b and c) The glycan bound near the N-terminus viewed from two different angles, with the residues at the binding interface shown. Molecular graphics was created using UCSF Chimera. Hydrogen bonds are shown by dotted cyan lines. Tryptophan 18 (W18) is colored in magenta.

Fig. 3. Covalent imprinting of 4-nitrophenyl α-d-mannopyranoside using 4-vinylphenylboronic acid as the FM to afford a molecularly imprinted polymer (MIP) with an imprinted binding site depicted schematically.

Fig. 4. Preparation of an SA-imprinted shell on silica core particles. (Adapted with permission from ref. . Copyright 2015, the American Chemical Society.)

Fig. 5. (a) Functionalization of glass beads with GlcA templates by the click reaction. (b and c) Confocal images of fixed human keratinocytes showing extracellular, intracellular, and nuclear labeling by MIPGlcA-NPs (red) and by HABP/streptavidin FITC (green). The nuclei are stained blue with Hoechst. Scale bar = 20 μm. (Adapted with permission from ref. . Copyright 2019, the Nature Publishing Group.)

Fig. 6. (a) Boronate affinity-based controllable oriented surface imprinting of glycoproteins. (Reproduced with permission from ref. . Copyright 2014, the Royal Society of Chemistry.) (b) Boronate-affinity glycan-oriented surface imprinting for producing glycan-imprinted MNPs. (Reproduced with permission from ref. . Copyright 2015, John Wiley & Sons, Inc.)

Fig. 7. (a) Micellar imprinting. (b) MINP with boroxole binding group in the imprinted site, with the boronate-forming hydroxyls colored red. (Adapted with permission from ref. . Copyright 2021, the American Chemical Society.)

Fig. 8. Schematic representation of MBAm-functionalized MINP to bind 4-nitrophenyl-α-d-glucopyranoside 16.

Fig. 9. (a) Preparation of artificial glycosidase MINP(p-G1 + 18d) and its binding of maltose. (b) Product distribution (G1, G2, and G3) in the hydrolysis of amylose by the MINP catalysts after 24 h at 60 °C in H₂O, with the reaction mixture (1.0 mL) dialyzed against 40 mL of deionized water using a membrane (MWCO = 500). [Amylose] = 1 mg mL⁻¹, [MINP] = 20 μM. (c) Recyclability of MINP(G2 + 18h) in maltohexaose hydrolysis. [Maltohexaose] = 100 μM. [MINP] = 20 μM. (Adapted with permission from ref. . Copyright 2021, the Royal Society of Chemistry.)

Fig. 10. (a) Comparison of reducing sugar formed during hydrolysis of cellulose by the synthetic MINP catalysts in 2 : 8 [C₂mim]OAc/DMSO with 5% H₂O at 90 °C and natural cellulase in NaOAc buffer pH 5.0 at 37 °C. [Cellulose] = 8 mg mL⁻¹. [Catalyst] = 2 mg mL⁻¹. (b) Recyclability of MINP(19 + 18f) on magnetic nanoparticles for cellulose hydrolysis. (Adapted with permission from ref. . Copyright 2021, the American Chemical Society.)

Yan Zhao