Syntheses, Conformations and X‐Ray Structure Analyses of the Saccharide Chains from the Core Regions of Glycoproteins

Abstract

The covalently bound carbohydrate moiety in glycoproteins can stabilize the protein molecule intramolecularly, or it may have an intermolecular function as receptor in biological recognition. The discovery of these biological phenomena has led to a renaissance of the chemistry and biochemistry of carbohydrates. Both N‐glycoproteins as well as O‐glycoproteins contain special, invariant oligosaccharide chains in the protein‐binding region, which occur again in all glycoproteins, and are described as the “core regions.” This review describes the various methods of oligosaccharide synthesis that may be used to arrive at the basic core structures by chemical means. Methods of oligosaccharide synthesis have improved so much that it is possible to synthesize complex lactosamine‐type structures, and “bisected”‐type structures up to nona‐ and undecasaccharides respectively. Oligosaccharide chains are considerably less flexible than peptide chains. Using modern methods of NMR spectroscopy, their preferred solution conformation can readily be determined. In the case of one branched octasaccharide, a comparison of the conformations in solution and in the crystal is possible. Oligosaccharides may be linked to the amide group of an asparagine, or to the hydroxyl groups of serine or threonine. By using suitable protecting groups, the glycosyl amino acids obtained can be extended with further amino acids at the N‐ or C‐terminus, thus arriving at the desired glycopeptide sequences. In the linkage region, glycopeptides prefer certain conformations. Future research into glycoprotein functions may involve the synthesis and biochemical study of modified glycoprotein segments.

Conformational investigations on glycosylated threonine-oligopeptides of increasing chain length

“…The onset of a g-turn conformation, not frequently observed in DMSO [10], could be forced by the sterically demanding requirements of the glycosylated and deacetylated Thr residues [26]. In this connection it is worth pointing out that sugars are frequently found in turn regions of proteins [27].…”

Transferred Nuclear Overhauser Enhancement (NOE) and Rotating‐Frame NOE Experiments Reflect the Size of the Bound Segment of the Forssman Pentasaccharide in the Binding Site of Dolichos Biflorus Lectin

“…The Forssman pentasaccharide was obtained by chemical synthesis (Paulsen andBiinsch, 1980, 1981). The D. bzyorus Iectin was extracted and purified as described before (Etzler and Kabat, 1970 All 'H-NMR spectra were recorded on a Bruker DMX 600 NMR spectrometer using UXNMR and XWINNMR software (Bruker).…”

“…One reason for this discrepancy is the still limited availability of larger saccharide ligands. Although methods of synthetic carbohydrate chemistry and isolation techniques to obtain oligosaccharides from natural sources have been greatly refined during the past two decades (Schmidt, 1986;Paulsen, 1990;Thiem, 1995), it is still a difficult task in many cases to obtain substantial amounts of pentasaccharides or larger oligomers.…”

Glycopeptide Synthesis

“…Kunz (1987) has reviewed the solution synthesis of small glycopeptides by C-and N-terminal elongation of suitably protected building blocks by solution methods. Furthermore, some limited reviews essentially describing the work of particular groups have been published (Paulsen et al, 1988a;Kunz, 1984;Paulsen, 1990;Kunz and Brill, 1992;Meldal et al, 1992). This review does not cover the synthesis of bacterial cell wall peptidoglycan peptides, which has been reviewed by Lefrancier and Lederer (1981) and by Baschang (1989).…”