Toward fully synthetic glycoproteins by ultimately convergent routes: a solution to a long-standing problem.
A method is disclosed for the convergent synthesis of multiply glycosylated peptides. The approach centers on a convergent technique for generating masked, complex glycopeptide-containing C-terminal acyl donors. Activation of the latent donor in situ and use directly in segment coupling with a second peptide bearing a complex carbohydrate produces a completely unprotected, bifunctional glycopeptide. The system demonstrates a minimum level of hydrolysis and epimerization at the C-terminal amino acid residue of the acyl donor during fully convergent segment coupling and is therefore a powerful tool for the synthesis of glycoproteins.
Warren
J David
JD
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
Miller
Justin S
JS
Keding
Stacy J
SJ
Danishefsky
Samuel J
SJ
D000215:Acylation; D000595:Amino Acid Sequence; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004921:Erythropoietin / Q000737:chemistry; D006023:Glycoproteins / Q000138:chemical synthesis*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry; D011487:Protein Conformation
D006023:Glycoproteins; D011134:Polysaccharides; D004921:Erythropoietin