Correction: The challenges of glycan recognition with natural and artificial receptors.

Correction for 'The challenges of glycan recognition with natural and artificial receptors' by Stefano Tommasone et al., Chem. Soc. Rev., 2019, 48, 5488-5505.

Targeting Oligosaccharides and Glycoconjugates Using Superselective Binding Scaffolds.

Recognition of oligosaccharides is associated with very limited specificity due to their strong solvation in water and the high degree of subtle structural variations between them. Here, oligosaccharide recognition sites are created on material surfaces with unmatched, binary on-off binding behavior, sharply discriminating a target oligosaccharide over closely related carbohydrate structures. The basis for the superselective binding behavior relies on the highly efficient generation of a pure, high order complex of the oligosaccharide target with synthetic carbohydrate receptor sites, in which the spatial arrangement of the multiple receptors in the complex is preserved upon material surface incorporation. The synthetic binding scaffolds can easily be tailored to recognize different oligosaccharides and glycoconjugates, opening up a realm of possibilities for their use in a wide field of applications, ranging from life sciences to diagnostics.

Cooperative Multipoint Recognition of Sialic Acid by Benzoboroxole-Based Receptors Bearing Cationic Hydrogen-Bond Donors.

Sialic acid recognition remains an interesting and challenging target in molecular receptor design. Herein, we report a series of benzoboroxole-based receptors in which cationic hydrogen-bond donors have been introduced and shown to promote multipoint sialic acid recognition. One striking feature revealed by these receptors is that the carboxylate sialic acid residue is the primary binding determinant for recognition by benzoboroxole, in which the presence of charge-reinforced hydrogen bonds results in enhanced selectivity for sialic acid over other carbohydrates and a 4.5-fold increase in affinity. These findings open up wide possibilities for benzoboroxole-based receptors use in life science research, biotechnology, and diagnostics.

The challenges of glycan recognition with natural and artificial receptors.

Glycans - simple or complex carbohydrates - play key roles as recognition determinants and modulators of numerous physiological and pathological processes. Thus, many biotechnological, diagnostic and therapeutic opportunities abound for molecular recognition entities that can bind glycans with high selectivity and affinity. This review begins with an overview of the current biologically and synthetically derived glycan-binding scaffolds that include antibodies, lectins, aptamers and boronic acid-based entities. It is followed by a more detailed discussion on various aspects of their generation, structure and recognition properties. It serves as the basis for highlighting recent key developments and technical challenges that must be overcome in order to fully deal with the specific recognition of a highly diverse and complex range of glycan structures.

Biomolecular Fishing for Calixarene Partners by a Chemoproteomic Approach.

MS-based chemical-proteomics technology is introduced herein as a third general strategy to study the biomolecular recognition properties of given calixarene derivatives. In particular, we demonstrate that a simply designed calix[4]arene derivative 1 a bearing acetamido groups at the exo rim (pAC), when linked to a solid support, is able to fish out a specific protein (PDI protein) from a crude extract of HeLa cells. Western blot and surface plasmon resonance studies confirmed the direct interaction between PDI and the linker-free pAC derivative 1 b with considerable affinity, and in vitro tests showed its inhibition of PDI chaperone activity. In accordance with the role of PDI in a variety of human cancers, biological tests showed that pAC 1 b was cytotoxic and cytostatic toward CAL-27 and PC-3 cancer cell lines in vitro. Docking studies showed that H bonds and hydrophobic interactions contribute to the stabilization of the PDI/pAC complex.

Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters.

A set of 6- to 24-valent clusters was constructed with terminal deoxynojirimycin (DNJ) inhibitory heads through C6 or C9 linkers by way of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions between mono- or trivalent azido-armed iminosugars and calix[8]arene scaffolds differing in their valency and their rigidity but not in their size. The power of multivalency to upgrade the inhibition potency of the weak DNJ inhibitor (monovalent DNJ Ki being at 322 and 188 µM for C6 or C9 linkers, respectively) was evaluated on the model glycosidase Jack Bean α-mannosidase (JBα-man). Although for the clusters with the shorter C6 linker the rigidity of the scaffold was essential, these parameters had no influence for clusters with C9 chains: all of them showed rather good relative affinity enhancements per inhibitory epitopes between 70 and 160 highlighting the sound combination of the calix[8]arene core and the long alkyl arms. Preliminary docking studies were performed to get insights into the preferred binding modes.

Precise Generation of Selective Surface-Confined Glycoprotein Recognition Sites.

Since glycoproteins have become increasingly recognized as key players in a wide variety of disease processes, there is an increasing need for advanced affinity materials for highly selective glycoprotein binding. Herein, for the first time, a surface-initiated controlled radical polymerization is integrated with supramolecular templating and molecular imprinting to yield highly reproducible synthetic recognition sites on surfaces with dissociation constants (K D) in the low micromolar range for target glycoproteins and minimal binding to nontarget glycoproteins. Importantly, it is shown that the synthetic strategy has a remarkable ability to distinguish the glycosylated and nonglycosylated forms of the same glycoprotein, with a >5-fold difference in binding affinity. The precise control over the polymer film thickness and positioning of multiple carbohydrate receptors plays a crucial role in achieving an enhanced affinity and selectivity. The generated functional materials of unprecedented glycoprotein recognition performance open up a wealth of opportunities in the biotechnological and biomedical fields.

Reversible, High-Affinity Surface Capturing of Proteins Directed by Supramolecular Assembly.

The ability to design surfaces with reversible, high-affinity protein binding sites represents a significant step forward in the advancement of analytical methods for diverse biochemical and biomedical applications. Herein, we report a dynamic supramolecular strategy to directly assemble proteins on surfaces based on multivalent host-guest interactions. The host-guest interactions are achieved by one-step nanofabrication of a well-oriented ß-cyclodextrin host-derived self-assembled monolayer on gold (ß-CD-SAM) that forms specific inclusion complexes with hydrophobic amino acids located on the surface of the protein. Cytochrome c, insulin, α-chymotrypsin, and RNase A are used as model guest proteins. Surface plasmon resonance and static time-of-flight secondary ion mass spectrometry studies demonstrate that all four proteins interact with the ß-CD-SAM in a specific manner via the hydrophobic amino acids on the surface of the protein. The ß-CD-SAMs bind the proteins with high nanomolar to single-digit micromolar dissociation constants ( KD). Importantly, while the proteins can be captured with high affinity, their release from the surface can be achieved under very mild conditions. Our results expose the great advantages of using a supramolecular approach for controlling protein immobilization, in which the strategy described herein provides unprecedented opportunities to create advanced bioanalytic and biosensor technologies.

On-Demand Electrical Switching of Antibody-Antigen Binding on Surfaces.

The development of stimuli-responsive interfaces between synthetic materials and biological systems is providing the unprecedented ability to modulate biomolecular interactions for a diverse range of biotechnological and biomedical applications. Antibody-antigen binding interactions are at the heart of many biosensing platforms, but no attempts have been made yet to control antibody-antigen binding in an on-demand fashion. Herein, a molecular surface was designed and developed that utilizes an electric potential to drive a conformational change in surface bound peptide moiety, to give on-demand control over antigen-antibody interactions on sensor chips. The molecularly engineered surfaces allow for propagation of conformational changes from the molecular switching unit to a distal progesterone antigen, resulting in promotion (ON state) or inhibition (OFF state) of progesterone antibody binding. The approach presented here can be generally applicable to other antigen-antibody systems and meets the technological needs for in situ long-term assessment of biological processes and disease monitoring on-demand.