Self-Assembling Peptides Improve the Stability of Glucagon-like Peptide-1 by Forming a Stable and Sustained Complex

Abstract

The multiple physiological characterizations of glucagon-like peptide-1 (GLP-1) make it a promising drug candidate for the treatment of T2DM. However, the short half-life of GLP-1 limits its clinical utility. Self-assembling peptides are presumed to wrap GLP-1 peptide, and this helps to prolong the stability of GLP-1 consequently. The aim of this study was to investigate whether self-assembling peptides could be applied to prolong the half-life of GLP-1 as sustained release preparations. In this study, five different self-assembling peptides were employed. The formation of the complexes was monitored using gel filtration and mass spectrometry and was simulated by Molecular Dynamics. Stabilization, insulin secretion stimulation, and glucose tolerance tests were performed to investigate the physiological characteristics retained by GLP-1 following complex formation with self-assembling peptides. Our findings revealed that, among the five different self-assembling peptides tested, complex of Pep-1 and GLP-1 exhibited a remarkable extension in the half-life of GLP-1. In addition, the experimental animals treated with a GLP-1/Pep-1 complex exhibited better blood glucose clearance activity over a greater duration of time than the animals treated with GLP-1 alone. Based on our results, an adjustment of the Pep-1 and GLP-1 ratios is presumed to be able to control the half-life of GLP-1 (e.g., medium-acting and long-acting). Collectively, the findings in this study suggest that the self-assembling peptide Pep-1 could serve as a powerful drug preparation tool to extend the short half-life of therapeutic peptides.