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Improved strategies for synthesis make it possible to expand the range of glycopeptides available for detailed conformational studies. The glycopeptide 1 was synthesized using a new solid phase synthesis of carbohydrates and a convergent coupling to peptide followed by deprotection. Its conformational properties were subjected to NMR analysis and compared with a control peptide 2 prepared by conventional solid phase methods. Whereas peptide 2 fails to manifest any appreciable secondary structure, the glycopeptide 1 does show considerable conformational bias suggestive of an equilibrium between an ordered and a random state. The implications of this ordering effect for the larger issue of protein folding are considered.Although glycosylation of many natural products is a widespread phenomenon, the consequences of this modification on the molecular properties of proteins are not well understood. An intriguing possibility is that glycosylation of the protein effects the conformation of the nascent chain and influences its rate of folding (1-3). In spite of this and many other outstanding issues pertaining to glycosylated species, studies have been relatively few due to the limited availability of suitable material and model compounds. Some relief is now being realized with improvements in methodology for synthesis of oligosaccharides and glycopeptides (4-11). For instance, access to the glycopeptide 1 studied here (vide infra) is a consequence of these advances (12). Its pentapeptide segment was designed to incorporate the Asn-Xxx-Thr consensus sequence for N-glycosylation, and a trisaccharide was linked through the side chain amide of the asparagine residue to the peptide.A detailed picture of the organization of a pendant oligosaccharide on a fully folded protein in solution has been obtained from the recent study of the glycosylated CD2 protein (13). However, in trying to determine the extent to which glycosylation influences early stages of the protein folding process, glycopeptides provide more appropriate models since the conformation of the system is not dominated by the overall fold of the ultimately organized protein structure. Some recent studies on glycopeptides have provided insights into potential conformational consequences of glycosylation for both .In the case of O-linked glycopeptides (14,15,20), NMR studies have shown that the peptide backbone responds to glycosylation, as evidenced by changes in sequential amideamide nuclear Overhauser effect (NOE) interactions. The response is further modulated by whether the sugar component is a mono-or disaccharide. Direct evidence for local interaction between sugar and peptide backbone has been indicated by the existence of an NOE crosspeak between the amide proton of the N-acetylglucosamine attached to the O-linked residue and the backbone amide of the threonine to which the sugar was attached (14). In the case of N-linked species in aqueous solution, fluorescence energy transfer and NMR studies support the notion of a change in the distribution of ...

Oligosaccharides and glycopeptides are of considerable importance in molecular biology and pharmacology. However, their synthesis is complicated by the large number of different linking sites between each saccharide unit, the need for stereochemical control, the chemical sensitivity of the glycopeptide bonds, and the need to harmonize diverse protecting groups. Here, an efficient solid-phase synthesis of three N-linked glycopeptides based on glycal assembly is presented. The peptide domain can be extended while the ensemble remains bound to the polymer. The glycopeptides synthesized here are among the largest N-linked glycopeptides ever accessed by either solution- or solid-phase synthesis.

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El A barrier for racemization in excess of 60 kcdl mol ~ was reported for a tetra-ophenylene derivative: P. Rashidi-Ranjbar, Y -M. Man, J. Sandstrom, H. N. C .Wong.

Polymer-supported synthesis of 2,Fi-disubstituted tetrahydrofurans via tandem 1,3-dipoIar cycloadditiodelectrophilic cyclization has been accomplished using a five-step reaction sequence to give 2-(cyanomethyl)-5-(iodomethyl)tetrahydrofuran (cis:truns ratio of 1:2) in 40% overall yield. The corresponding 2-(cyanomethyl)-6-(iodomethyl)tetrahydropyran was similarly formed in a 7% overall yield. The final electrophilic cyclization simultaneously releases the desired product and regenerates the initial polymer-bound functionality. In the process the desired cyclic ether is obtained exclusively; byproducts of the sequence are not cleaved from the polymer support. In addition the polymer support is sufficiently robust to be recovered and recycled through the reaction sequence.

Solid-supported synthesis can be conducted to produce a variety of glycopeptides in good overall yields. The carbohydrates are formed by the glycal assembly method. The polymer-bound construct terminates in a glycal. The terminal double bond can be functionalized to provide a C2−N-acetyl glucosamine linkage with an amino group in the anomeric position. The latter can be coupled, in a convergent manner, to the γ-carboxyl group of an aspartyl residue on a preformed peptide. Iodosulfonamidation of the polymer-bound glucal to the N-acetyl glucosamine using anthracenesulfonamide was crucial for the success of the solid-phase synthesis. This general method was employed in the formation of a variety of glycopeptides.

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