TY - JOUR
T1 - Glycoinsulins
T2 - Dendritic sialyloligosaccharide-displaying insulins showing a prolonged blood-sugar-lowering activity
AU - Sato, Masaaki
AU - Furuike, Tetsuya
AU - Sadamoto, Reiko
AU - Fujitani, Naoki
AU - Nakahara, Taku
AU - Niikura, Kenichi
AU - Monde, Kenji
AU - Kondo, Hirosato
AU - Nishimura, Shin Ichiro
PY - 2004/11/3
Y1 - 2004/11/3
N2 - Mono-, di-, and trisialyloligosaccharides were introduced to mutant insulins through enzymatic reactions. Sugar chains were sialylated by α2,6-sialyltransferase (α2,6-SiaT) via an accessible glutamine residue at the N-terminus of the B-chain attached by transglutaminase (TGase). Sia2,6-di-LacNAc-Ins(B-F1Q) and Sia2,6-tri-LacNAc-Ins(B-F1Q), displaying two and three sialyl-N-acetyllactosamines, respectively, were administered to hyperglycemic mice. Both branched glycoinsulins showed prolonged glucose-lowering effects compared to native or lactose-carrying insulins, showing that sialic acid is important in obtaining a prolonged effect. Sia2,6-tri-LacNAc-Ins(B-F1Q), in particular, induced a significant delay in the recovery of glucose levels.
AB - Mono-, di-, and trisialyloligosaccharides were introduced to mutant insulins through enzymatic reactions. Sugar chains were sialylated by α2,6-sialyltransferase (α2,6-SiaT) via an accessible glutamine residue at the N-terminus of the B-chain attached by transglutaminase (TGase). Sia2,6-di-LacNAc-Ins(B-F1Q) and Sia2,6-tri-LacNAc-Ins(B-F1Q), displaying two and three sialyl-N-acetyllactosamines, respectively, were administered to hyperglycemic mice. Both branched glycoinsulins showed prolonged glucose-lowering effects compared to native or lactose-carrying insulins, showing that sialic acid is important in obtaining a prolonged effect. Sia2,6-tri-LacNAc-Ins(B-F1Q), in particular, induced a significant delay in the recovery of glucose levels.
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U2 - 10.1021/ja046426l
DO - 10.1021/ja046426l
M3 - Article
C2 - 15506764
AN - SCOPUS:7444266855
SN - 0002-7863
VL - 126
SP - 14013
EP - 14022
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 43
ER -