Glycopeptide and Oligosaccharide Libraries

Abstract

Despite the burgeoning interest in the various biological functions and consequent therapeutic potential of the vast number of oligosaccharides found in nature on glycoproteins and cell surfaces, the development of combinatorial carbohydrate chemistry has not progressed as rapidly as expected. The reason for this imbalance is rooted in the difficulty of oligosaccharide assembly and analysis that renders synthesis a rather cumbersome endeavor. Parallel approaches that generate series of analogous compounds rather than real libraries have therefore typically been used. Since generally low affinity is obtained for interactions between carbohydrate receptors and modified oligosaccharides designed as mimetics of natural carbohydrate ligands, glycopeptides have been explored as alternative mimics. Glycopeptides have been proven in many cases to be superior ligands with higher affinity for a receptor than the natural carbohydrate ligand. High-affinity glycopeptide ligands have been found for several types of receptors including the E-, P-, and L-selectins, toxins, glycohydrolases, bacterial adhesins, and the mannose-6-phosphate receptor. Furthermore, the assembly of glycopeptides is considerably more facile than that of oligosaccharides and the process can be adapted to combinatorial synthesis with either glycosylated amino acid building blocks or by direct glycosylation of peptide templates. The application of the split and combine approach using ladder synthesis has allowed the generation of very large numbers of compounds which could be analyzed and screened for binding of receptors on solid phase. This powerful technique can be used generally for the identification and analysis of the complex interaction between the carbohydrates and their receptors.

Progress in Thioaptamer Development

“…Selection from one-bead one-compound libraries [90] based on split synthesis methods [104][105] offers an attractive alternative to in vitro combinatorial selection methods and has been demonstrated for organic molecules [106], peptides [13,90,[104][105] and oligosaccharide libraries in the 1990's [14,[107][108][109]. Remarkably, the onebead one-ODN combinatorial library selection methodology has only recently been demonstrated [110].…”

Natural Product‐Like Combinatorial Libraries

“…24 So far, combinatorial chemistry of carbohydrates has been mainly focused on the solid and solution-phase synthesis of oligosaccharide libraries, as well as glycomimetics, and several articles have reviewed this area. 31,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] A few examples are highlighted in the section.…”

Solid-Phase Synthesis of α-Gal Epitopes: On-Resin Analysis of Solid-Phase Oligosaccharide Synthesis with 19F NMR Spectroscopy

“…However, the functions of carbohydrates found in glycoconjugates such as glycoproteins and glycolipids are less well understood. Increased attention is therefore directed toward generation of protocols for solid-phase synthesis, which will permit preparation of the biologically interesting, and highly diverse, oligosaccharides on an individual basis or in the form of libraries. − Despite the considerable progress made during recent years, − the assembly of complex oligosaccharides on solid support still constitutes a substantial challenge.…”