Synthesis of the glycosyl amino acids N alpha-Fmoc-Ser[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-OPfp and N alpha-Fmoc-Thr[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-OPfp and the application in the solid-phase peptide synthesis of multiply glycosylated mucin peptides with Tn and T antigenic structures.
Two new glycosyl amino acids N alpha-Fmoc-Ser[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-+ ++OPfp and N alpha-Fmoc-Thr[Ac4-beta-D-Galp-(1-->3)-Ac2-alpha-D-GalN3p]-+ ++OPfp were synthesized. Glycosylation of N alpha-Fmoc-Ser-OPfp or N alpha-Fmoc-Thr-OPfp with protected beta-D-Gal-(1-->3)-D-GalN3 donors afforded the glycosyl amino acids containing an activated C-terminus which could be utilized directly for solid-phase glycopeptide synthesis. The transformation of the 2-azido group into the acetamido derivative was achieved quantitatively at the end of the synthesis by treatment of the polymer-bound glycopeptide with thioacetic acid. The versatility of this strategy was demonstrated by the assembly of eight triply glycosylated mucin peptides which were synthesized simultaneously by multiple column techniques. The glycopeptides were prepared in order to investigate the substrate specificity of a galactosyltransferase.
Paulsen
H
H
Institut für Organische Chemie der Universität Hamburg, Germany.
Peters
S
S
Bielfeldt
T
T
Meldal
M
M
Bock
K
K
D000595:Amino Acid Sequence; D000941:Antigens; D001386:Azides / Q000737:chemistry; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000138:chemical synthesis*; D005690:Galactose / Q000737:chemistry; D006020:Glycopeptides / Q000138:chemical synthesis*; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009077:Mucins / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology; D012694:Serine / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
D000941:Antigens; D001386:Azides; D004187:Disaccharides; D006020:Glycopeptides; D009077:Mucins; D013912:Threonine; D012694:Serine; D005690:Galactose