Accelerated solid-phase synthesis of glycopeptides containing multipleN-glycosylated sites

Abstract

Peptide fragments of glycoproteins containing multiple N-glycosylated sites are essential biochemical tools not only to investigate protein-protein interactions but also to develop glycopeptide-based diagnostics and immunotherapy. However, solid-phase synthesis of...

Chemoenzymatic Synthesis of Glycopeptides to Explore the Role of Mucin 1 Glycosylation in Cell Adhesion

“…We applied Fmoc/ t Bu/OAc solid‐phase peptide synthesis (SPPS) for the efficient preparation of the MUC1 tandem repeat aglycone 1 and of the three differently glycosylated variants 2 , 3 , and 4 , carrying one, two, and three GalNAc monosaccharides, respectively, at specific Thr and/or Ser residues in the sequence (Scheme 1 and Figures S1–S4 in the Supporting Information). Fmoc−Thr[GalNAc(OAc) 3 ]−OH and Fmoc−Ser[GalNAc(OAc) 3 ]−OH were used as building blocks in SPPS to introduce O ‐glycosylation directly with complete control over position [29] …”

Transport phenomena in solid phase synthesis supported by cross-linked polymer beads

“…More recently, Bakhatan et al , 57 Naoum et al , 25,58 Alshanski et al , 26 and Strauss et al 27 reported higher yields in the SPS of peptides, glycopeptides, and glycans using mechanical stirring rather than gas bubbling; this improvement is attributed to the fact that mechanical stirring “increases the diffusion of both reagents and beads in a narrow dimension reactor”. 25 No distinction between external and internal diffusion was made.…”

“…20,21 The need for further optimization regarding process time, cost, and yield, especially in AGA, has prompted renewed attention to the physical aspects of SPS, such as mixing and swelling. [22][23][24][25][26][27] Glycans are branched structures where regioand stereocontrol must be controlled throughout the synthesis. Consequently, carbohydrate building blocks are more complex and expensive than the precursors of linear molecules such as oligonucleotides and peptides.…”

“…Recent strategies to achieve reaction acceleration included microwave radiation, 24,29,30 dual temperature control systems, 24 pre-heating the reagents, 28,31 and highshear mixing methods. [25][26][27]32 However, little attention has been paid to formal modeling and understanding the transport phenomena behind such technological developments.…”