Platform Synthetic Lectins for Divalent Carbohydrate Recognition in Water

Abstract

Biomimetic carbohydrate receptors (“synthetic lectins”) have potential as agents for biological research and medicine. However, although effective strategies are available for “all‐equatorial” carbohydrates (glucose, etc.), the recognition of other types of saccharide under natural (aqueous) conditions is less well developed. Herein we report a new approach based on a pyrene platform with polar arches extending from aryl substituents. The receptors are compatible with axially substituted carbohydrates, and also feature two identical binding sites, thus mimicking the multivalency observed for natural lectins. A variant with negative charges forms 1:2 host/guest complexes with aminosugars, with K 1>3000 m −1 for axially substituted mannosamine, whereas a positively charged version binds the important α‐sialyl unit with K 1≈1300 m −1.

A Potent Mimetic of the Siglec‐8 Ligand 6’‐Sulfo‐Sialyl Lewisx

“…Hydrogen bonds are depicted as dashed lines. The individual fragments, the galactose derivative 9 and the neuraminic acid derivative 10, [44] as well as the disaccharides 11-13 with modified glycerol side chains (for the synthesis see Supporting Information) did not show any affinity. The hydrogen bond network, the glycerol side chain is involved in ( Figure 1B), obviously plays an important role in the binding process.…”

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).…”

Biomimetic Carbohydrate‐Binding Agents (CBAs): Binding Affinities and Biological Activities

“…Only in the last decade have biomimetic CBAs exhibiting affinities comparable with those of natural lectins (and therefore called “synthetic lectins”) been reported. In particular, very good affinities towards charged saccharides—both cationic, such as aminosugars, and anionic, such as N ‐acetylneuraminic acid (Neu5Ac)—have been reported, thanks to the use of complementary charged receptors. In contrast, effective recognition of neutral saccharides is considerably more complicated.…”