Molecular Engineering of Carbohydrate Recognition

Abstract

Carbohydrates play a number of structural, functional, and metabolic roles in underpinning natural life processes, acting in states of both health and disease. Given this importance, over millions of years of evolution, living systems have developed an ability to recognize and bind carbohydrates, achieving remarkable recognition affinity and specificity in spite of the often hydrophilic and ubiquitous character of carbohydrate targets. In recent years, bio‐inspired synthetic receptors have been developed to bind carbohydrates, with examples of (pseudo)temple‐shaped receptors, flexible receptors, and dynamic‐covalent/coordinative receptors reported. Certain of these have even demonstrated promising results, for example in binding glucose or exhibiting antiviral and antibiotic function. Accordingly, and in spite of remaining challenges, the development of synthetic receptors for carbohydrate recognition holds great promise to combat some of the most urgent problems facing our world today.

Towards Biomimetic Recognition of Glycans by Synthetic Receptors

“…Since the first example developed by Aoyama in 1988, [38] this heterogeneous group of small molecules, tailored-made for carbohydrate recognition, has grown extensively to achieve effective binding properties and selectivity in the recognition of biologically relevant saccharides. [39,40] The successful use of biomimetic CBAs in a biological context has further raised interest in the topic, which is still a hot field of current research. [25,41] However, development of effective biomimetic receptors that have to compete with a polar solvent such as water is indeed a non-trivial task.…”

A Macrocyclic Tweezers‐Shaped Receptor for the Biomimetic Recognition of the Gal(α1‐3)Gal Disaccharide of the α‐Gal Antigen

“…[11] Following a biomimetic approach, based exclusively on non-covalent interactions, the investigation of synthetic receptors for carbohydrates has long been restricted to organic solvents, where polar interactions are enhanced by the mild competition of solvent molecules. [12] Indeed, water poses a serious obstacle to the recognition of polar species such as carbohydrates, [13][14][15] and biomimetic receptors effective in water have only recently been on the rise in the literature. [4,16] While the use of "temple" architectures has given good results in terms of affinity and selectivity in water toward all-equatorial carbohydrates like glucose, [17,18] there are few examples in the literature of receptors capable of recognizing in water biologically relevant mono-and oligosaccharides with axial substituents and/or α-glycosidic linkages.…”