Solid-phase synthesis of core 2 O-linked glycopeptide and its enzymatic sialylation

Abstract

The core 2-type tetrasaccharide building blocks ( 1a / 1b ) for solid-phase synthesis of glycopeptide were synthesized via stereoselective glycosylation of the disaccharyl Ser/Thr ( 3a / 3b ) with a glycosyl fluoride ( 2 ) carrying the 2-trichloroacetamido group that was readily converted into a 2-acetamido group by reduction. A segment of glycoprotein leukosialin (215–224) was synthesized by the solid-phase protocol, the building block ( 1b ) being utilized. Cleavage of the synthetic glycopeptide from resin was effected with reagent K and subsequent treatment of the product with a cocktail for the ‘low-acidity TfOH’ facilitated complete removal of the benzyl groups with minimum loss of glycosidic linkages. To the deprotected glycopeptide ( 21 ), were enzymatically introduced N-acetylneuraminic acid (sialic acid) residues in remarkably high efficiency by using the specific sialyltransferases.