Specific molecular recognition is routine for biology, but has proved difficult to achieve in synthetic systems. Carbohydrate substrates are especially challenging, because of their diversity and similarity to water, the biological solvent. Here we report a synthetic receptor for glucose, which is biomimetic in both design and capabilities. The core structure is simple and symmetrical, yet provides a cavity which almost perfectly complements the all-equatorial β-pyranoside substrate. The affinity for glucose, at Ka ~18,000 M-1 , compares well with natural receptor systems. Selectivities also reach biological levels. Most other saccharides are bound ~100 times more weakly, while non-carbohydrate substrates are ignored. Glucose-binding molecules are required for initiatives in diabetes treatment, such as continuous glucose monitoring and glucose-responsive insulin. The performance and tunablity of this system augur well for such applications.

General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms A threading receptor for polysaccharides Polysaccharides are the dominant organic molecules in the biosphere 1 , and thus key renewable resources 2,3 . However the most abundant, including cellulose and chitin, are generally the most difficult to utilise due to extreme insolubility. At present there is no method for mobilising these materials in water under mild conditions, so that modifications involve chemical transformations in aggressive media [4][5][6] or the slow action of enzymes on undissolved solids 7 . Dissolution in aqueous media at biological pH would allow new paths to exploitation. In particular, the polysaccharides could be exposed to enzymes, either natural or engineered, to which they would be far more vulnerable. The rapid conversion of cellulose to glucose is just one prospective outcome.Here we adumbrate a strategy for the dissolution of cellulose, and related polysaccharides, through the application of synthetic receptors. The approach employs cage molecules with amphiphilic interiors, complementary to the carbohydrate targets. Critically the receptors are able to thread onto the polysaccharides, forming polypseudorotaxanes 8,9 . Because of the threaded topology, many receptor molecules can bind to one polysaccharide chain, surrounding the polymer with hydrophilic groups. If binding is sufficiently strong to counteract crystal packing forces, dissolution should be feasible. We report the design and synthesis of a threading receptor for polysaccharides, and show that it forms pseudorotaxanes with water-soluble oligosaccharides.We also describe evidence for polypseudorotaxane formation from polysaccharides under certain conditions. The results demonstrate the feasibility of polysaccharide threading in water, and could point the way to systems capable of solubilisation.A defining feature of cellulose 1 and chitin 2 (Fig. 1a) is the all-equatorial disposition of intra-chain linkages and polar substituents and (consequently) the axial positioning of apolar CH groups. In the extended conformation of the polymer, this creates two parallel strips of hydrophobic surface separated by lines of hydrogen-bonding functional groups. Our strategy for complementing these supramolecular valencies is illustrated in Fig. 1b. We sought a cage-like receptor structure in which two aromatic surfaces would be held parallel to each other, separated by rigid, polar spacers. The portals of the cage would be large enough to allow threading by the polysaccharide substrates. The aromatic surfaces would be capable of forming hydrophobic and CH-π interactions with axial CH groups in the substrates, while polar groups would hydrogen bond to equatorial substituents.We had previously used a related approach to bind all-equatorial mono-and di-saccharides in water 10-13 .However, these earlier designs e...

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water‐soluble carbohydrate receptors (“synthetic lectins”). Both systems show outstanding affinities for derivatives of N‐acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc‐β‐OMe with K a≈20 000 m −1, whereas the other one binds an O‐GlcNAcylated peptide with K a≈70 000 m −1. These values substantially exceed those usually measured for GlcNAc‐binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl–peptide complex can be explained by extra‐cavity interactions, raising the possibility of a family of complementary receptors for O‐GlcNAc in different contexts.

These chiral “synthetic lectins” are the first to discriminate between carbohydrate enantiomers, and also show unprecedented affinities for monosaccharide substrates.