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 ha...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2010-08, Vol.20 (15), p.4631-4634
Hauptverfasser:	Ueda, Taichi, Ito, Takaomi, Tomita, Kazuyoshi, Togame, Hiroko, Fumoto, Masataka, Asakura, Kenji, Oshima, Takeo, Nishimura, Shin-Ichiro, Hanasaki, Kohji
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Sequence Animals Biological and medical sciences Blood Glucose - metabolism Chemoenzymatic synthesis Diabetes Mellitus, Type 2 - drug therapy Disease Models, Animal General and cellular metabolism. Vitamins Glucagon-Like Peptide 1 - antagonists & inhibitors Glucagon-Like Peptide 1 - metabolism Glycoconjugate Glycosylation Hypoglycemic Agents - chemistry Hypoglycemic Agents - therapeutic use Incretin hormone Medical sciences Mice Molecular Sequence Data Peptide drug Peptides - chemistry Peptides - therapeutic use Pharmacology. Drug treatments Venoms - chemistry Venoms - therapeutic use
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Zusammenfassung:	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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2010.06.002