Glycoinsulins: dendritic sialyloligosaccharide-displaying insulins showing a prolonged blood-sugar-lowering activity.
Mono-, di-, and trisialyloligosaccharides were introduced to mutant insulins through enzymatic reactions. Sugar chains were sialylated by alpha2,6-sialyltransferase (alpha2,6-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.
Sato
Masaaki
M
Division of Biological Sciences, Graduate School of Science, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan.
Furuike
Tetsuya
T
Sadamoto
Reiko
R
Fujitani
Naoki
N
Nakahara
Taku
T
Niikura
Kenichi
K
Monde
Kenji
K
Kondo
Hirosato
H
Nishimura
Shin-Ichiro
S
D041721:3T3-L1 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D005973:Glutamine / Q000737:chemistry / Q000378:metabolism; D006023:Glycoproteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006031:Glycosylation; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D011972:Receptor, Insulin / Q000378:metabolism
D001786:Blood Glucose; D006023:Glycoproteins; D007328:Insulin; D009844:Oligosaccharides; C016735:sialooligosaccharides; D005973:Glutamine; D011972:Receptor, Insulin