Glycopeptides of biological interest: A challenge for chemical synthesis

Abstract

The synthesis of glycopeptides which constitute partial structures of glycoproteins, e. g. tumor-associated antigens or virus envelope glycoproteins, is presented. The problems of the selective deblocking and chain extension of such glycopeptides which contain acetalic glycosidic bonds were solved by application of the fluorenylmethoxycarbonyl (Fmoc) group cleavable with the weak base morpholine and by the introduction of the allylic protecting groups which can be removed under almost neutral conditions via palladium(0)-catalyzed allyl transfer to weakly basic nucleophiles. The allylic protection was extended to a new allylic anchoring principle in the solid phase synthesis. It allows to detach the synthesized peptides and glycopeptides from the polymer under neutral conditions. The synthesis of glycopeptides with branched and fucose containing saccharide side chains demands an even more chemoselective strategy which includes the exchange of protecting groups within the saccharide portion. In these syntheses, the azido group was used as the protection and precursor of the anomeric amino function required for the construction of the N-glycosyl asparagine linkage. An important indirect protecting effect is exhibited by the O-acetyl protecting groups within the saccharide part which strongly stabilize the glycosidic bonds. Using these methods, glycopeptides which contain tumor-associated TN and T antigen or Lewis antigen-type side chains and represent partial sequences of virus envelope proteins were synthesized and linked to carrier proteins to give synthetic glycoprotein antigens. © 1993 IUPAC