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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chromatography, High Pressure Liquid
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Diabetes Mellitus, Experimental / drug therapy
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Diabetes Mellitus, Type 2 / drug therapy*
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Drug Stability
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Evans Blue / chemistry*
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Exenatide
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Humans
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Hypoglycemic Agents / chemistry
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Hypoglycemic Agents / pharmacokinetics
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Hypoglycemic Agents / pharmacology*
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Maleimides / chemistry
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Mice, Inbred C57BL
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Naphthalenesulfonates / chemistry
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Naphthalenesulfonates / pharmacology*
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Peptides / chemistry
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Peptides / pharmacology*
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Serum Albumin / chemistry
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Venoms / chemistry
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Venoms / pharmacology*
Substances
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Abextide II
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Hypoglycemic Agents
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Maleimides
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Naphthalenesulfonates
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Peptides
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Serum Albumin
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Venoms
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maleimide
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Evans Blue
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Exenatide