title: Identification of glycosylated exendin-4 analogue with prolonged blood glucose-lowering activity through glycosylation scanning substitution.
abstract: 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.
authors.affiliation: Discovery Research Laboratories, Shionogi and Co., Ltd, Fukushima-ku, Osaka, Japan. taichi.ueda@shionogi.co.jp
authors.forename: Taichi
authors.initials: T
authors.lastname: Ueda
authors.forename: Takaomi
authors.initials: T
authors.lastname: Ito
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tomita
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togame
authors.forename: Masataka
authors.initials: M
authors.lastname: Fumoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Asakura
authors.forename: Takeo
authors.initials: T
authors.lastname: Oshima
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Nishimura
authors.forename: Kohji
authors.initials: K
authors.lastname: Hanasaki
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide