Chemistry: A European Journal 2007-01-01

An approach for a synthesis of asparagine-linked sialylglycopeptides having intact and homogeneous complex-type undecadisialyloligosaccharides.

Naoki Yamamoto, Ayumi Takayanagi, Ayako Yoshino, Tohru Sakakibara, Yasuhiro Kajihara

Index: Chemistry 13(2) , 613-25, (2007)

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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.