Glycosylation of Fmoc amino acids: preparation of mono- and di-glycosylated derivatives and their incorporation into Arg-Gly-Asp (RGD)-containing glycopeptides

Abstract

Compounds containing O-glycosidic linkages between carbohydrate species (D-glucopyranose, D-mannopyranose and L-rhamnopyranose) and hydroxy-containing amino acid components (L-threonine, L-serine and L-hydroxyproline) have been synthesized. Significant quantities of disaccharide-containing by-products have been isolated and identified from reactions involving 2,3,4,6-tetraacetyl-α-D-glucopyranosyl bromide. With other sugar derivatives (D-mannose and L-rhamnose), the yields of these disaccharide-containing amino acid products are very much reduced.The glycoamino acids have been incorporated into linear peptides containing the Arg-Gly-Asp (RGD) sequence in high yields by using solid-phase Fmoc-based methodology. In addition, cyclic glycopeptides containing cystine residues have been synthesized.The synthesized glycopeptides are found to be equipotent with, or slightly less potent than, the corresponding non-glycosylated parent peptides on testing as platelet aggregation inhibitors.

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