Cooperativity of carbohydrate moiety orientation and beta-turn stability is determined by intramolecular hydrogen bonds in protected glycopeptide models

The 2,3,4,6-Tetra-O-acetyl-beta-D-gluco-, and beta-D-galactopyranosides, as well as approximately 4:1 anomeric mixtures of alpha- and beta-mannopyranosides of Boc-X-Y-NHCH3 dipeptides (X-Y = Pro-Ser, Pro-D-Ser, Val-Ser, Val-D-Ser, and Gly-Ser) have been synthesized. CD and ir spectroscopic studies were performed to characterize the conformation of the glycosylated peptide backbone and examine the possible formation of intrapeptide and glycopeptide intramolecular H-bonds. It was found that O-glycosylated peptides containing a D-serine residue are likely to adopt a type II beta-turn while those with the Pro-Ser or Val-Ser sequence feature a type I (III) beta-turn in solution. Glycosylation also increases the magnitude of the CD bands, characteristic of the given type of beta-turns, which can be interpreted as an indication of the stabilization of the folded backbone conformation. Infrared data showed that in nonpolar solutions the peracetyl glycopeptides adopt both single- and double H-bonded conformations whose ratio, in some cases, depends on the position at C-2' of the H-bond acceptor acetoxy group. These data suggest that five-, seven-, or ten-membered glyco-turns may play an important role in fixing the steric orientation of the carbohydrate antennae systems in glycoproteins.