Synthesis and conformational analysis of N-glycopeptides that contain extended sugar chains

Maltooligosaccharides with 2–7 sugar moieties were converted into β-1-amino-1-deoxy derivatives and were coupled to Nα-fluorenylmethoxycarbonyl-L-aspartic acid α-tert-butyl β-pentafluorophenyl ester. After trifluoroacetic acid deprotection, the resulting glycosylated asparagines were used as building blocks for the solid-phase synthesis of T-ceIl epitopic glycopeptide analogues. The coupling efficiencies of the glycoanimo acid synthons and the acid and base stability of the resulting glycopeptides indicate the applicability of this solid-phase synthetic protocol for the incorporation of sugars that are comparable in size with that of the natural carbohydrate antennae of N-glycoproteins. The sugars placed into N-terminal position did not affect the strong α-helical structure of the peptides, but inhibited the disulfide-bridge formation of proximal cysteine residues in a carbohydrate length-dependent manner.