Chemo-enzymatic synthesis of the glucagon containing N-linked oligosaccharide and its characterization. (2nd January 2018)

• Record Type: Journal Article
• Authors: Higashiyama, Takayuki; Umekawa, Midori; Nagao, Masaya; Katoh, Toshihiko; Ashida, Hisashi; Yamamoto, Kenji
• Is Part Of: Carbohydrate research. Volume 455(2017)
• Page Start: 92
• Page End: 96
• Publication Date: 2018-01-02
• Subjects: Glucagon -- Chemo-enzymatic synthesis -- Sialo-oligosaccharide oxazoline -- Transglycosylation -- Endo-M; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2017.11.007
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: The chemo-enzymatic synthesis of an artificially N-glycosylated derivative of glucagon, a peptide hormone that regulates the blood sugar level, is described. We synthesized the glycosylated glucagon by chemical synthesis of an N -acetylglucosaminyl peptide and enzymatic transfer of an oligosaccharide using the transglycosylation activity of the glycosynthase-like mutant of Mucor hiemalis endo-β- N -acetylglucosaminidase (Endo-M) and sialo-oligosaccharide oxazoline as a donor substrate. The sialo-oligosaccharide-attached glucagon synthesized showed high resistance against protease degradation and stimulated the release of glucose from mouse hepatocytes when added to cells. The synthetic glucagon showed slightly higher activity than native glucagon and has potential as a therapeutic agent for treating diabetic patients. Graphical abstract: Highlights: Glucagon with an N-linked oligosaccharide was chemo-enzymatically synthesized. Biological activity of glycosylated glucagon was higher than native glucagon. Glycosylated glucagon was highly resistant to protease and peptidase digestions.