An accessible bicyclic architecture for synthetic lectins

Abstract

Bicyclic carbohydrate receptors are easier to synthesise than tri- or tetra-cyclic relatives, and are better adapted to bind monosaccharide residues with bulky appendages. Disaccharides containing β-glucosyl units are preferred substrates.

Binding Studies on a Library of Induced‐Fit Synthetic Carbohydrate Receptors with Mannoside Selectivity

“…This receptor demonstrates the potential of flexible scaffolds for addressing the unmet challenge of creating synthetic carbohydrate receptors that possess non‐glucosidic selectivities. Davis et al., using an anthracene‐based receptor, have subsequently confirmed the value of incorporating conformational flexibility in receptor design as a route to increasing binding affinity . Building upon this result, they subsequently reported a pyrene‐based synthetic carbohydrate receptor that binds some axially substituted pyranosides in water, whose negatively charged variant forms 1:2 host–guest complexes with aminosugars, with K 1 of ≈3.0×10 3 m −1 for d ‐mannosamine.…”

“…Davis et al, using an anthracene-based receptor,h ave subsequently confirmed the value of incorporating conformational flexibility in receptor design as ar oute to increasing binding affinity. [32] Building upon this result,t hey subsequently reported a pyrene-based synthetic carbohydrate receptor that binds some axially substitutedp yranosides in water,w hose negatively charged variant forms 1:2h ost-guest complexes with aminosugars, with K 1 of % 3.0 10 3 m À1 for d-mannosamine. In turn, a positivelyc harged variant binds a-sialyl units with K 1 of % 1.3 10 3 m À1 .…”

Molecular cages for biological applications

“…Carbohydrate recognition represents a formidable challenge for binding in aqueous media. Davis' group has long been working in a series of cages able to bind monosaccharides 47,48 and disaccharides [49][50][51] using polycyclic compounds. The general strategy that the group has developed consists in preparing hosts with the 'temple' design.…”

A Water Soluble Pd2L4 Cage for Selective Binding of Neu5Ac

“…For example, macrocycle 4 (Figure 1c, left) [13] is highly selective for GlcNAc‐β‐OMe ( K a ≈18,000 M −1 in water) by encapsulating the carbohydrate by regular HBs and CH ⋅⋅⋅ π interactions [17] . However, such covalent macrocycles are not selective for Neu5Ac or related anionic carbohydrates [16c–e] . This can be rationalized by the presence of anionic dendrimers (R 2 ) used to solubilize the hydrophobic binding pockets.…”

“… [17] However, such covalent macrocycles are not selective for Neu5Ac or related anionic carbohydrates. [ 16c , 16d , 16e ] This can be rationalized by the presence of anionic dendrimers (R 2 ) used to solubilize the hydrophobic binding pockets.…”