Saccharide Recognition by a Three‐Arm‐Shaped Host Having Preorganized Three‐Dimensional Hydrogen‐Bonding Sites

Abstract

Generally, cage‐shaped hosts for saccharides can bind strongly to guest molecules because of the three‐dimensional preorganized hydrogen‐bonding sites. However, the preparation of cage molecules is often difficult because of the low yield of the macrocyclization step. Here, we report a three‐arm‐shaped molecule possessing pyridine‐acetylene‐phenol units as a new kind of host having a preorganized three‐dimensional hydrogen‐bonding site. This three‐arm‐shaped host was readily prepared compared to a cage‐shaped analogue. This host associated with lipophilic glycosides to form chiral complexes, and the association constants were sufficiently high as to be comparable to those of the cage‐shaped analogue. Furthermore, this host extracted native monosaccharides into a lipophilic solvent.

Binding modes of methyl α-d-glucopyranoside to an artificial receptor in crystalline complexes

“…Beside the above mentioned crystalline complexes of acyclic receptors, 1,6 the crystal structures of foldamers 7 a – d and of a macrocyclic receptor 8 with a bound sugar molecule are described in the literature and contribute to a better understanding of the basic molecular features of carbohydrate recognition (for recent examples of binding studies in solution, see ref. 9 ). In contrast, a large number of X-ray crystal structures of proteins bound to various sugar substrates has been described in the literature 10,11 and represents an important source of information about the noncovalent interactions that contribute to the selective and effective binding of carbohydrates by proteins.…”

Pillar[5]arene-Derived endo-Functionalized Molecular Tube for Mimicking Protein–Ligand Interactions

“…Recently, several biomimetic pockets with polar binding sites in their hydrophobic pockets have been disclosed. − Impressively, the thermodynamics of interactions between biomimetic pockets and guests in water have been studied systematically by Jiang and co-workers, − and the work is highly valuable as ligand recognition by protein binding pockets occur in an aqueous environment in living systems. Notwithstanding, it is challenging to assess the contribution to pocket-ligand binding affinity “solely” from hydrogen bonding only through studies of the complexation in water.…”

“…Therefore, to imitate the microenvironment within protein binding pockets, the interior surface of the biomimetic receptors must possess polar functionalities for H-bond formation. To this end, there have been reports of pocket-shaped receptors, − such as cavitands, glucose receptor 2, aryl-extended calix[4]­pyrrole receptors, and helical aromatic and oligoamide foldamers (Figure a–e). , Jiang’s group recently made significant progress in transforming naphthalene-based tubular molecules into biomimetic tubes in which the inwardly directed functional groups improved their binding affinity and selectivity toward fragment ligands (Figure f). − As a class of tubular-shaped macrocyclic hosts, pillar­[ n ]­arenes − could seat various functional substituents on their rims, for instance, amino acids or short peptides, for mimicking transmembrane channels . Nonetheless, all of these rim-embedded polar functional substituents pointed outward, and there has been no report about the mounting polar functionalities pointing inward into the cavity cores of pillar­[ n ]­arenes.…”

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

“…[22,23] Indeed, milestones in this field have been achieved only recently, mainly by means of sophisticated macrocyclic architectures. [24][25][26][27][28][29][30] In contrast, acyclic receptors have been largely unexplored, [31][32][33][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.…”