Both authors contributed equally to this work.
Development of a C-Terminal Site-Specific PEGylated Analog of GLP-1 with Improved Anti-Diabetic Effects in Diabetic Mice
Article first published online: 16 JAN 2013
© 2013 Wiley Periodicals, Inc.
Drug Development Research
Volume 74, Issue 3, pages 186–193, May 2013
How to Cite
Gao, M., Tong, Y., Gao, X. and Yao, W. (2013), Development of a C-Terminal Site-Specific PEGylated Analog of GLP-1 with Improved Anti-Diabetic Effects in Diabetic Mice. Drug Dev. Res., 74: 186–193. doi: 10.1002/ddr.21059
- Issue published online: 10 APR 2013
- Article first published online: 16 JAN 2013
- Manuscript Accepted: 11 DEC 2012
- Manuscript Received: 6 NOV 2012
- China National Natural Science Foundation. Grant Numbers: 81172974, 30973667
- National S&T Project. Grant Number: 2012ZX09103101-016
- Jiangsu Province “Qing Lan Project”
- Jiangsu Province “333 High-level Talents Cultivation Project”
- glucagon-like peptide-1;
Glucagon-like peptide-1 (GLP-1) is an attractive lead for antidiabetic drug development but its utility is limited due to poor in vivo stability. In this study, we developed a C-terminal site-specific PEGylated analog of GLP-1 based on the structure-activity relationship of GLP-1. Using three steps of chromatography, we obtained the conjugate with a high purity. Polyethylene glycol (PEG) conjugation greatly enhanced GLP-1 potency in vivo without changing its original conformation. In streptozotosin diabetic mice, this conjugate had an improved antidiabetic effect, as measured by fasting glucose/insulin/glycosylated serum protein, oral glucose tolerance test, and histochemical studies. Additionally, this PEG-conjugated peptide delayed gastric emptying without significant effects on body weight gain. Our data indicate that this conjugate may be a promising lead for the development of antidiabetic drugs.