Stable Evans Blue Derived Exendin-4 Peptide for Type 2 Diabetes Treatment.

Abstract

In the treatment of type 2 diabetes mellitus, it is very important to develop therapeutics with prolonged circulation half-life. Exendin-4 is a glucagon like peptide-1 receptor (GLP-1R) agonist that has been modified in different ways for imaging insulinoma and for treating type-2 diabetes. In this work, we synthesized a maleimide derivative of truncated Evans blue dye (MEB-C3-Mal) to conjugate with (Cys(40))exendin-4 to obtain a highly stable MEB-C3-(Cys(40))exendin-4 (denoted as Abextide II). Through in situ binding with endogenous albumin, Abextide II lowers blood glucose level and prolongs the hypoglycemic effect in a type 2 diabetes mouse model more than the FDA approved Albiglutide.

• Authors: Yi Liu, Guohao Wang, Huimin Zhang, Ying Ma, Lixin Lang, Orit Jacobson, Dale O Kiesewetter, Lei Zhu, Shi Gao, Qingjie Ma, Xiaoyuan Chen
• Journal: Bioconjugate chemistry (Bioconjug Chem) Vol. 27 Issue 1 Pg. 54-8 (Jan 20 2016) ISSN: 1520-4812 [Electronic] United States
• PMID: 26641886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Abextide II
• Hypoglycemic Agents
• Maleimides
• Naphthalenesulfonates
• Peptides
• Serum Albumin
• Venoms
• maleimide
• Evans Blue
• Exenatide

Topics

• Animals
• Chromatography, High Pressure Liquid
• Diabetes Mellitus, Experimental (drug therapy)
• Diabetes Mellitus, Type 2 (drug therapy)
• Drug Stability
• Evans Blue (chemistry)
• Exenatide
• Humans
• Hypoglycemic Agents (chemistry, pharmacokinetics, pharmacology)
• Maleimides (chemistry)
• Mice, Inbred C57BL
• Naphthalenesulfonates (chemistry, pharmacology)
• Peptides (chemistry, pharmacology)
• Serum Albumin (chemistry)
• Venoms (chemistry, pharmacology)