Solid-phase synthesis of peptide and glycopeptide thioesters through side-chain-anchoring strategies.
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.
Ficht
Simon
S
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Payne
Richard J
RJ
Guy
Richard T
RT
Wong
Chi-Huey
CH
D020650:Combinatorial Chemistry Techniques; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D006020:Glycopeptides / Q000737:chemistry*; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D004952:Esters; D006020:Glycopeptides; D010455:Peptides; D013438:Sulfhydryl Compounds