A biomimetic receptor for glucose

Abstract

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.

Diabetes Treatment: Selective Synthetic Receptor for Glucose

“…In a recent development, they at the University of Bristol and the company Ziylo (a new company name, Carbometrics) have achieved a remarkable improvement on past performance. They disclose a synthetic receptor that selectively recognizes glucose in aqueous biological media with affinities for far stronger than their previously reported systems for carbohydrate recognition (see Figure ) . The new receptor is also highly selective, showing hundred times greater affinities for glucose as compared to closely related molecules such as mannose or galactose.…”

“…They disclose a synthetic receptor that selectively recognizes glucose in aqueous biological media with affinities for far stronger than their previously reported systems for carbohydrate recognition (see Figure 2). [7] The new receptor is also highly selective, showing 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 hundred times greater affinities for glucose as compared to closely related molecules such as mannose or galactose.…”

“…The triethylmesitylene units are colored pale blue, and the dendritic side-chains are omitted for clarity. Reproduced with permission from Ref [7]. Copyright (2018) Nature Publishing Group.…”

“…Synthetic route to receptor 2. [7] NMR and Isothermal Titration Calorimetry (ITC) titrations were performed to measure affinities of receptor 2 with a variety of substrates. From NMR titrations, the binding constant for glucose was quantified as K a = 18,600 M À 1 and ITC showed similar affinity for glucose (K a = 18,200 M À 1 ).…”

Synthesis of Pashinintide A, a Natural Cyclic Hexapeptide Supposedly Capable of Forming a Complex with Sucrose

“…[2] Indeed, design and synthesis of artificial receptors for carbohydrates has been intensively pursued by chemists; works from the Davis group are prominent examples in this area. [3][4][5][6][7] Many synthetic receptors have been designed based on easily available chiral building blocks, such as oligosaccharides, cyclodextrins, peptides, and steroidal units. [8][9][10][11] An interesting example was reported by Kubik et al that synthetic cyclohexapeptides could bind selectively to methyl α-D-glucopyranoside through interactions between the hydroxyl groups of the pyranoside and the carboxylate groups installed on the peripheral of the symetrical cyclopeptide ( Figure 1A).…”