Premium
Solid‐Phase Synthesis of Peptide and Glycopeptide Thioesters through Side‐Chain‐Anchoring Strategies
Author(s) -
Ficht Simon,
Payne Richard J.,
Guy Richard T.,
Wong ChiHuey
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200701978
Subject(s) - side chain , glycopeptide , peptide , anchoring , chemistry , combinatorial chemistry , biochemistry , organic chemistry , psychology , cognitive science , polymer , antibiotics
An efficient new strategy for the synthesis of peptide and glycopeptide thioesters is described. The method relies on the side‐chain immobilization of a variety of Fmoc‐amino acids, protected at their C‐termini, on solid supports. Once anchored, peptides were constructed using solid‐phase peptide synthesis according to the Fmoc protocol. After unmasking the C‐terminal carboxylate, either thiols or amino acid thioesters were coupled to afford, after cleavage, peptide and glycopeptide thioesters in high yields. Using this method a significant proportion of the proteinogenic amino acids could be incorporated as C‐terminal amino acid residues, therefore providing access to a large number of potential targets that can serve as acyl donors in subsequent ligation reactions. The utility of this methodology was exemplified in the synthesis of a 28 amino acid glycopeptide thioester, which was further elaborated to an N‐terminal fragment of the glycoprotein erythropoietin (EPO) by native chemical ligation.