Application of serine- and threonine-derived cyclic sulfamidates for the preparation of S-linked glycosyl amino acids in solution- and solid-phase peptide synthesis.
Cyclic sulfamidates were synthesized in 60% yield from L-serine and allo-L-threonine, respectively. These sulfamidates reacted with a variety of unprotected 1-thio sugars in aqueous bicarbonate buffer (pH 8) to afford the corresponding S-linked serine- and threonine-glycosyl amino acids with good diastereoselectivity (> or =97%) after hydrolysis of the N-sulfates. The serine-derived sulfamidate was incorporated into a simple dipeptide to generate a reactive dipeptide substrate that underwent chemoselective ligation with a 1-thio sugar to afford an S-linked glycopeptide. This sulfamidate was also incorporated into a peptide on a solid support in conjunction with solid-phase peptide synthesis. Chemoselective ligation of a 1-thio sugar with the cyclic sulfamidate was achieved on the solid support, followed by removal of the N-sulfate. Finally, the peptide chain of the resulting support-bound S-linked glycopeptide was extended using standard peptide synthesis procedures.
Cohen
Scott B
SB
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309-0215, USA.
Halcomb
Randall L
RL
D000596:Amino Acids / Q000138:chemical synthesis*; D006020:Glycopeptides / Q000138:chemical synthesis; D006031:Glycosylation; D010455:Peptides / Q000138:chemical synthesis*; D012694:Serine / Q000031:analogs & derivatives*; D012996:Solutions; D013449:Sulfonamides / Q000737:chemistry*; D013912:Threonine / Q000031:analogs & derivatives*
D000596:Amino Acids; D006020:Glycopeptides; D010455:Peptides; D012996:Solutions; D013449:Sulfonamides; D013912:Threonine; D012694:Serine