Specific Recognition of Disaccharides in Water by an Artificial Bicyclic Carbohydrate Receptor

Abstract

We present the synthesis of a peptide-based bicyclic carbohydrate receptor capable of carbohydrate recognition in 10 % deuterated acetic acid in water. The binding constants were estimated by using NMR spectroscopy, and furthermore, aThe most abundant class of organic molecules on earth is that of the carbohydrates. They serve as structural materials in the form of cellulose or chitin, for example, and as energy storage to provide the fuels for biochemical processes. The class of carbohydrates covers protein and cell membranes, and carbohydrates act as signalling molecules that by interaction with receptors and lectins determine the fate of these. Carbohydrates are implicated in cell differentiation, in cancer immunology as well as in host defence against viruses, bacteria and parasites. By interaction with numerous receptors in membranes or with secondary receptor sites on functional macromolecules, carbohydrates determine the distribution and architecture of functional macromolecular assemblies and bring together growth hormones, receptors, proteases and so on. [1] This important set of functionalities renders carbohydrate recognition an attractive target for artificial receptors. Selective artificial carbohydrate receptors could be used either diagnostically to determine the location and concentration of a particular carbohydrate structure, for example, the concentration of glucose in blood, or as a drug targeting compound functioning as an artificial antibody. In some instances an artificial receptor could even be a drug in itself by blockage of carbohydrate-mediated viral entry or bacterial adhesion.Diabetes will, according to WHO, affect more than 360 million people in the world by 2030 (http://www.who.int/ mediacentre/factsheets/fs312/en/index.html), and therefore [a]

Progress in biomimetic carbohydrate recognition

“…The smaller substrate maltose 30 caused similar effects but appeared to bind less strongly (K a * 1 M -1 ). A more elaborate peptidic design 50 was described by the group of Meldal [95]. The bicyclic structure incorporates a macrocyclic dodecapeptide with a naphthyl bridge, providing an amphiphilic cavity not unlike that of a natural lectin.…”

Sugar Recognition: Designing Artificial Receptors for Applications in Biological Diagnostics and Imaging

“…In combination with these aromatic platforms, a number of hydrogen bond donor/acceptor arrays have been systematically surveyed to identify and optimize those most likely to remain effective upon introduction into competitive media. One array type that has shown promise for later use in aqueous media is that offered by the semi‐rigid amide backbones of natural amino acids and peptides 17a,d. Through pairing of amide, amine, or imine motifs with other moieties such as indole,18a imidazole,18a pyridine,14a pyrimidine,14a naphthyridine,18b pyrrole,18c catechol,18d or acetal,18e a number of artificial arrays have been developed.…”

Oligosaccharide Sensing in Aqueous Media by Porphyrin–Curdlan Conjugates: A Prêt‐á‐Porter Rather Than Haute‐Couture Approach

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Indeed, simultaneously achieving satisfactory selectivity and sensitivity for at arget saccharide is an urgentd emand in medicalp ractice,b ut the saccharide stereochemical diversity, heavy hydration,a nd low physiological concentration (typically 5mm)h ave allowed only limited success in developingg ood chemosensors for mono-and disaccharide operative in aqueous media. [27][28][29][30][31][32][33][34][35][36][37][38][39] Apparentlyi nspired by Nature's strategy, both the approaches have been effectiveinconstructing avariety of rationally designed architectures with ac onfining cavity decorated with well preorganized functional groups to optimize the covalent/noncovalent interactions with the target saccharides. [27][28][29][30][31][32][33][34][35][36][37][38][39] Apparentlyi nspired by Nature's strategy, both the approaches have been effectiveinconstructing avariety of rationally design...…”