A convergent strategy for the preparation of N-glycan core di-, tri-, and pentasaccharide thioaldoses for the site-specific glycosylation of peptides and proteins bearing free cysteines

摘要: Abstract Mammalian glycoprotein biosynthesis produces heterogeneous ranges of proteins that possess the same peptide backbone but differ in nature and site glycosylation. This feature has frustrated efforts to develop therapeutic glycoproteins as well elucidation biological functions individual glycoforms. We have developed an attractive approach well-defined glycoforms by oxidative coupling thioaldoses cysteine-containing peptides give disulfide-linked neoglycoconjugates. To this end, chemical synthesis di-, tri-, pentasaccharide N-glycan was undertaken. A convergent used for preparation containing a ‘synthetically difficult’ β-mannoside linkage. linkage installed forming initially corresponding β-glucoside-containing pentasaccharide, followed inversion configuration at C-2. exploited levulonyl ester C-2 glucosyl donor, which directed β-glucoside exclusively could be removed selectively using hydrazine acetate without affecting other base-labile functionalities. The resulting alcohol converted into triflate, displaced tri-n-butylammonium β-mannosidic trisaccharide prepared similar manner. Thioaldoses were displacing peracetylated α-glycosyl chlorides with thioacetate β-thioacetates, upon saponification gave desired compounds. incubation molar excesses chitobiose thioaldose glutathione BSA resulted site-specific formation neoglycopeptide neoglycoprotein, respectively.