Identification of glycosylated exendin-4 analogue with prolonged blood glucose-lowering activity through glycosylation scanning substitution

Taichi Ueda; Takaomi Ito; Kazuyoshi Tomita; Hiroko Togame; Masataka Fumoto; Kenji Asakura; Takeo Oshima; Shin-Ichiro Nishimura; Kohji Hanasaki

doi:10.1016/j.bmcl.2010.06.002

Identification of glycosylated exendin-4 analogue with prolonged blood glucose-lowering activity through glycosylation scanning substitution

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4631-4. doi: 10.1016/j.bmcl.2010.06.002. Epub 2010 Jun 4.

Authors

Taichi Ueda¹, Takaomi Ito, Kazuyoshi Tomita, Hiroko Togame, Masataka Fumoto, Kenji Asakura, Takeo Oshima, Shin-Ichiro Nishimura, Kohji Hanasaki

Affiliation

¹ Discovery Research Laboratories, Shionogi and Co., Ltd, Fukushima-ku, Osaka, Japan. taichi.ueda@shionogi.co.jp

PMID: 20576431
DOI: 10.1016/j.bmcl.2010.06.002

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.

MeSH terms

Amino Acid Sequence
Animals
Blood Glucose / metabolism*
Diabetes Mellitus, Type 2 / drug therapy
Disease Models, Animal
Exenatide
Glucagon-Like Peptide 1 / antagonists & inhibitors
Glucagon-Like Peptide 1 / metabolism
Glycosylation
Hypoglycemic Agents / chemistry*
Hypoglycemic Agents / therapeutic use
Mice
Molecular Sequence Data
Peptides / chemistry*
Peptides / therapeutic use
Venoms / chemistry*
Venoms / therapeutic use

Substances

Blood Glucose
Hypoglycemic Agents
Peptides
Venoms
Glucagon-Like Peptide 1
Exenatide