Synfacts 2019; 15(04): 0455
DOI: 10.1055/s-0037-1612281
Peptide Chemistry
© Georg Thieme Verlag Stuttgart · New York

Total Chemical Synthesis of a Glycoprotein by Native Chemical Ligation

Hisashi Yamamoto
Manthena Chaithanya
Shin Y, Winans KA, Backes BJ, Kent SB. H, Ellman JA, Bertozzi CR. * University of California, Berkeley and Gryphon Sciences, South San Francisco, USA
Fmoc-Based Synthesis of Peptide-αThioesters: Application to the Total Chemical Synthesis of a Glycoprotein by Native Chemical Ligation.

J. Am. Chem. Soc. 1999;
121: 11684-11689
Further Information

Publication History

Publication Date:
19 March 2019 (online)



The authors have developed a new approach for the synthesis of unprotected αthioesters by using Fmoc-based solid-phase peptide synthesis and have demonstrated its utility in the total synthesis of a glycosylated protein, the antimicrobial O-linked glycoprotein diptericin, by the native chemical ligation method. This method utilizes an alkanesulfonamide ‘safety-catch’ linker, which circumvented the problems associated with the incompatibility of glycosidic linkages with Boc chemistry and of thioesters with Fmoc chemistry.



The C-terminal residue of the peptide is attached to the resin through an acid- and base-stable N-acyl sulfonamide linkage. After peptide synthesis, the sulfonamide is activated by cyano­methylation and then cleaved with a thiol nucleo­phile. This general synthetic approach permits access to unprecedented quantities of homogeneous glycoproteins.