Chemoenzymatic Synthesis of O-Mannosylpeptides in Solution and on Solid Phase

Abstract

O-mannosyl glycans are known to play an important role in regulating the function of α-dystroglycan (α-DG), as defective glycosylation is associated with various phenotypes of congenital muscular dystrophy. Despite the well-established biological significance of these glycans, questions regarding their precise molecular function remain unanswered. Further biological investigation will require synthetic methods for the generation of pure samples of homogeneous glycopeptides with diverse sequences. Here we describe the first total syntheses of glycopeptides containing the tetrasaccharide NeuNAcα2-3Galβ1-4GlcNAcβ1-2Manα, which is reported to be the most abundant O-mannosyl glycan on α-DG. Our approach is based on biomimetic stepwise assembly from the reducing end and also gives access to the naturally occurring mono-, di-, and trisaccharide substructures. In addition to the total synthesis, we have developed a "one-pot" enzymatic cascade leading to the rapid synthesis of the target tetrasaccharide. Finally, solid-phase synthesis of the desired glycopeptides directly on a gold microarray platform is described.

Array-assisted Characterization of a Fucosyltransferase Required for the Biosynthesis of Complex Core Modifications of Nematode N-Glycans

“…However, the development of glycan arrays opens up new possibilities for examining these enzymes but to date has been (in terms of eukaryotic systems) limited to studying rather well characterized examples, such as mammalian fucosyl-and sialyltransferases or enzymes involved in plant cell wall biosynthesis (37)(38)(39)(40). On the other hand, glycosyltransferases have been useful in synthesis of glycan libraries subsequently printed onto arrays (41).…”

Preparation of Glycan Array and Its Applications

“…2i). The use of gold surface is also applicable to surface plasmon resonance and mass spectrometry study (Sardzik et al 2012). Moreover, the thiol group is known to react and conjugate with gold surface, so glycans modified with thiol group can be directly immobilized to gold surface (Fig.…”

Corrigendum to “The neoglycolipid (NGL)-based oligosaccharide microarray system poised to decipher the meta-glycome” [Curr Opin Chem Biol 18 (2014) 87–94]

“…A variety of immobilization strategies have been described for generation of the microarrays [1][2][3][4][5][6][7][8][9]. This review is focused on the neoglycolipid (NGL)-based microarray system developed in our laboratory, the first microarray system for sequence-defined oligosaccharides.…”