A Synthetic Galectin Mimic

Abstract

Galectins are a galactoside specific subclass of carbohydrate binding proteins (lectins) involved in various cellular activities, certain cancers, infections, inflammations, and many other biological processes. The molecular basis for the selectivity of galectins is well‐documented and revolves around appropriate interaction complementarity: an aromatic residue for C−H⋅⋅⋅π interactions and polar residues for (charge assisted) hydrogen bonds with the axial hydroxyl group of a galactoside. However, no synthetic mimics are currently available. We now report on the design and synthesis of the first galectin mimic (6), and show that it has a higher than 65‐fold preference for n‐octyl‐β‐galactoside (8) over n‐octyl‐β‐glucoside (7) in CD2Cl2 containing 5 % [D6]DMSO (with Ka≥4500 M−1 for 6:8). Molecular modeling informed by nOe studies reveal a high degree of interaction complementarity between 6 and galactoside 8, which is very similar to the interaction complementarity found in natural galectins.

Molecular Engineering of Carbohydrate Recognition

“…This investigation revealed that preorganization can adversely impact carbohydrate recognition. In addition, similar cages were prepared as synthetic Ca 2+ ‐dependent lectin mimics, [101] octyl mannoside receptors, [102] and synthetic galectin mimics [103] . Introducing four pendant guanidium chains as solubilizing groups, a water‐soluble cage was developed that could selectively recognize anionic monosaccharide N‐Acetylneuraminic acid (NANA) with moderate binding affinity [57] .…”

Biomimetic Tweezers for N‐Glycans: Selective Recognition of the Core GlcNAc2 Disaccharide of the Sialylglycopeptide SGP

“…However, achieving effective recognition of polar species like saccharides in water leveraging a biomimetic approach is a non‐trivial task [22,23] . Indeed, milestones in this field have been achieved only recently, mainly by means of sophisticated macrocyclic architectures [24–30] . In contrast, acyclic receptors have been largely unexplored, [31–34] although they may present distinct advantages over macrocyclic structures in terms of simpler synthesis, more easily modifiable structure, easy adaptability to different guests and, most of all, the possibility of binding non‐terminal saccharide entities.…”

Dynamic Approach to Synthetic Lectin for Glucose with Boosted Binding Affinity through C−H Hydrogen Bonds

“…Carbohydrate is a critical component in various biological processes, [1,2] such as energy storage, intercellular communication, and immune response. Synthetic receptors [3–11] that bind carbohydrates have the potential to facilitate the investigation of their biological functions and the creation of new therapeutic and diagnostic agents, such as anti‐infective agents, synthetic antibodies, and carbohydrate sensors. The development of synthetic receptors [12–14] for glucose, in particular, holds significant implications for managing blood glucose levels in diabetes.…”