Glycopeptides enzymatic solid-phase synthesis

Scheme 14.1 Strategies for glycopeptide library synthesis Strategy 1 chemical or enzymatic glycosylation of peptide or glycopeptide Strategy 2 the building-block approach. While enzymes have not yet been used in the solid-phase synthesis of glycopeptide libraries, several resin-bound glycopeptides have been glycosylated enzymatically.36,114...

Fig. 8. Enzymatic glycosylation in the solid-phase synthesis of oligosaccharides elongation of the glycopeptide with /M, 4-galactosyltrans-ferase and a-2,3-sialyltransferase. The glycopeptide is finally released by cleavage with a-chymotrypsin.

The enzymatic deprotection principle has also been applied in solid phase synthesis to create an anchoring structure that contains two cleavable positions an allylic ester on the one hand and a hydrophilic ester on the other hand. The release of j ptide using a palladium(O) catalyst delivers the peptide that is still bound to the hydrophilic structure. The carboxylic function can be liberated [48] using lipase catalysts (Fig. 32). This strategy was successfully demonstrated in the solid phase synthesis of peptides as well as O- and iV-glycopeptides [48]. 

SCHEME 11.2 Synthetic strategies of glycopeptides. (a) Convergent coupling, (b) solid-phase glycopeptide synthesis, and (c) enzymatic coupling. Asp, aspartic acid. 

Schuster M, Wang P, Paulson JC, Wong CH, Solid-phase chemical-enzymatic synthesis of glycopeptides and oligosaccharides, J. Am. Chem. Soc., 116 1135-6, 1994. 

Meldal, M, Auzanneau, F-I, Hindsgaul, O, Palcic, M M, A PEGA resin for use in the solid-phase chemical-enzymatic synthesis of glycopeptides, J. Chem. Soc. Chem. Commun., 1849-1850, 1994. 

A novel approach for the parallel synthesis of glycopeptides was suggested by Matsushita et al. (2013) by combining solid-phase peptide synthesis and dendrimer-supported enzymatic modifications. 

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