| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2006455 | Peptides | 2011 | 10 Pages |
The multiple physiological characterizations of glucagon-like peptide-1 (GLP-1) make it a promising drug candidate for the therapy of type 2 diabetes. However, the half-life of GLP-1 is short in vivo due to degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. This indicates that the stabilization of GLP-1 is critical for its utility in drug development. In this study, we developed a cluster of GLP-1 mutants containing an inter-disulfide bond that is predicted to increase the half-life of GLP-1 in vivo. Exendin-4 was also mutated with a disulfide bond similar to the GLP-1 analogs. In this study, the binding capacities of the mutants were determined, the stabilities of the mutants were investigated and the physiological functions of the mutants were compared with those of wild-type GLP-1 and exendin-4 in animals. The results indicated that the mutants remarkably raised the half-life in vivo; they also showed better glucose tolerance and higher HbA1c reduction than GLP-1 and exendin-4 in rodents. These results suggest that GLP-1 and exendin-4 mutants containing disulfide bonds might be utilized as possible potent anti-diabetic drugs in the treatment of type 2 diabetes mellitus.
► GLP-1 analog (GLP17057) containing an inter-disulfide bond extended its half-life. ► The analog (GLP17057) remained the biological activity of GLP-1. ► GLP17057 showed better glucose tolerance and higher HbA1c reduction than GLP-1 and Exendin-4. ► GLP17057 might be utilized as a long-lasting drug for type 2 diabetes.
