Novel Glucagon like peptide-1 (GLP-1) drugs were designed and industrially prepared by researchers at the Hefei Institutes of Physical Science of the Chinese Academy of Sciences through molecular design, strain construction, isolation and purification and animal experiments, according to a paper published in Pharmaceuticals.
"The GLP-1 analogs we developed boast with stable and hypoglycemic effects," said SUN Lei, first author of the paper.
GLP-1 can promote the pancreatic beta cells synthesis, insulin secretion and inhibition of glucagon release, which has a good therapeutic effect on type II diabetes. However, natural GLP-1 is easily degraded by dipeptidyl peptidase-4 (DPP-4) in human body, limiting its therapeutic effect on Type 2 diabetes mellitus. At present, the global output value of GLP-1 analogs has reached tens of billions of dollars, and highly stable GLP-1 drugs are a research hotspot.
In this study, on the basis of in-depth analysis of the molecular structure of human GLP-1, DPP-4 and GLP-1 receptors, a variety of GLP-1 analogs binding to the fusion protein fragments were designed, and then high-purity samples were prepared by industrial production.
Animal experiments showed that this GLP-1 analogue could effectively prevent the degradation of the DPP-4, and the hypoglycemic duration was more than 24 hours, indicating a high potential for commercial application.
This study provides a new way for the design and industrial production of novel protein drugs based on synthetic biology.
This work has been supported by the National Key R&D Program, the Anhui Provincial Science and Technology Major Project, and the Anhui Provincial Key R&D Program.
Molecular Docking between GLP-1 analogs and GLP-1 receptor and DPP-4. (Image by WANG Peng)
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