An Approach for a Synthesis of Asparagine‐Linked Sialylglycopeptides Having Intact and Homogeneous Complex‐Type Undecadisialyloligosaccharides

Abstract

This paper describes synthesis of asparagine-linked sialylglycopeptides. The typical feature of our strategy for the synthesis of a sialylglycopeptide is to employ undecadisialyloligosaccharyl Fmoc-asparagine (Fmoc-Asn(CHO)-OH) 1 without protecting groups on its hydroxyl groups except for the benzyl ester of the NeuAc residues. Our synthetic methodology solved the problem of esterification toward sugar hydroxyl groups by activated amino acids during the elongation of a peptide chain. When employing high concentrations of the Fmoc-amino acid, esterification markedly occurred, but the esterification scarcely occurred when employing low concentrations of reactants. Taking advantage of these findings, we examined the synthesis of a high molecular sialylglycopeptide, CTLA-4 fragment (113-150) 13 having two complex-type sialyloligosaccharides by use of native chemical ligation (NCL). As a result, we succeeded in the synthesis of a sialylglycopeptide having a cysteine residue at the N-terminus (CTLA-4: 129-150 fragment) 11 and a sialylglycopeptide-thioester (CTLA-4: 113-128 fragment) 12. Finally, the sialylglycopeptides synthesized were applied to NCL reactions. The reaction successfully afforded the desired product, CTLA-4 (113-150) 13 containing mature and pure complex-type sialyloligosaccharides in excellent purity.

Porous polymer particles—A comprehensive guide to synthesis, characterization, functionalization and applications

“…This chemistry is certainly as efficient as any well accepted click reaction. In addition to amidation, several highly efficient esterification strategies are also well established [372]. Various other peptide ligation strategies such as native chemical ligation [373] and Staudinger ligation [374] are well described in literature [375] but are kept out of the scope of this review.…”

Misfolded Glycoproteins as Probes for Analysis of Folding Sensor Enzyme UDP-Glucose

“…To obtain homogeneous glycoproteins, chemical synthesis has become an alternative method because of its dramatic advance in recent years (34)(35)(36)(37). Therefore, we examined the first chemical Fig.…”

The study of glycopeptide syntheses: exploring concise O-linked sialylglycopeptide synthesis and glycopeptide coupling reaction

“…For the synthesis of the sialyl-TN-MUC4 glycopeptide by solid phase peptide synthesis, we used 31, because we have already demonstrated the synthesis of N-linked glycopeptides by the use of an Fmoc-Asn-complex type oligosaccharide having a free sugar hydroxyl group (32). We thought that using this oligosaccharyl-amino acid 31 with the free hydroxyl group would avoid the deprotection step of the acetyl group under basic condition, which usually causes b-elimination of amino acids.…”

“…In terms of incorporation of 31, a conventional condition using DIPCDI and HOBt was used. The following amino acid residues were incorporated by the same reagents, but 40 mM concentration of amino acids was essential to avoid esteriˆcation of the sugarhydroxyl group on sialyl-TN (32). After construction of the glycopeptide, the glycopeptide was released from the resin by treatment with TFA/H2O (95:5) for 2 h. This condition aŠorded the desired sialylglycopeptide.…”