Identification of glycosylated exendin-4 analogue with prolonged blood glucose-lowering activity through glycosylation scanning substitution.
Exendin-4, a glucagon-like peptide 1 receptor agonist, is a potent therapeutic xenopeptide hormone for the treatment of type 2 diabetes. In order to further improve in vivo activity, we examined the introduction of sialyl N-acetyllactosamine (sialyl LacNAc) to exendin-4. The glycosylated analogue having sialyl LacNAc at position 28 was found to have improved in vivo activity with prolonged glucose-lowering activity.
Ueda
Taichi
T
Discovery Research Laboratories, Shionogi and Co., Ltd, Fukushima-ku, Osaka, Japan. taichi.ueda@shionogi.co.jp
Ito
Takaomi
T
Tomita
Kazuyoshi
K
Togame
Hiroko
H
Fumoto
Masataka
M
Asakura
Kenji
K
Oshima
Takeo
T
Nishimura
Shin-Ichiro
S
Hanasaki
Kohji
K
D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004195:Disease Models, Animal; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006031:Glycosylation; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000627:therapeutic use; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000627:therapeutic use; D014688:Venoms / Q000737:chemistry* / Q000627:therapeutic use
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide