A facile route to dynamic glycopeptide libraries based on disulfide-linked sugar–peptide coupling

We report here that disulfide-linked dynamic glycopeptide libraries can be constructed from 1-thiosugar and cysteine-rich oligopeptide building blocks upon gentle air oxidation of a slightly basic (pH 7.8) aqueous solution thereof. A mixture of 1-thiogalactose and two oligopeptides H2N–CysGlyCysGly–CO2H and H2N–GlyCycCysGlyGly–CO2H, for example, affords a poorly HPLC-resolved disulfide library composed of various sugar–peptide conjugates and cyclic peptides, at least 10 of which can be identified by ESI mass spectrometry. The building components of disulfide members are exchangeable with each other in the presence of dithiothreitol as an initiator to allow dynamic equilibration. A preliminary SPR examination shows that the thiogalactose-derived library indeed contains active divalent galactoside species capable of cross-linking peanut lectin molecules.