Synthesis of C-terminal glycopeptides from resin-bound glycosyl azides via a modified Staudinger reaction.
The solid-phase synthesis of glycopeptides containing the sugar at the C-terminus is reported. The method is demonstrated on a model, the endogenous antinociceptive peptide Leu-enkephalin. 2,3,4-Tri-O-acetyl-1-azido-1-deoxy-beta-D-glucopyranuronic acid was synthesized and immobilized onto a variety of derivatized resins. Conjugation of the first amino acid was accomplished by reaction of the resin-bound glycosyl azide with an activated amino acid, in one step, via a modified Staudinger reaction. Standard solid-phase peptide synthesis then resulted in the desired amide-linked glycopeptide. Reaction conditions and reagents for the glycosylation were varied to optimize the yield and purity of the product. The optimum conditions were found to be the use of a 4-fold molar excess of activated amino acid and 3-fold excess of tri-n-butylphosphine in tetrahydrofuran. This methodology is generally applicable to most peptide sequences and is compatible with both Boc- and Fmoc- synthetic strategies on a variety of resins.
Malkinson
J P
JP
Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, UK.
Falconer
R A
RA
Toth
I
I
D001386:Azides / Q000737:chemistry*; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment
D001386:Azides; D006020:Glycopeptides