GLP-1 drugs and purification process

Apr 08,2024

Bestchrom

GLP-1 (Glucagon-like peptide-1) drugs are a class of medications used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Overall, the purification process of GLP-1 drugs is a complex and highly regulated process aimed at producing high-quality medications for the treatment of diabetes and obesity.

GLP-1 and similar substance

Glucagon-like peptide(GLP-1) is an endogenous peptide hormone produced in the gut, promoting the secretion of insulin while inhibiting the secretion of glucagon. Glucagon-like peptide-1 receptor agonist(GLP-1RA)is GLP-1 analogue obtained by structural modification, lowering blood sugar by improving the active GLP-1 level in human body.

Upstream formation process

GLP-1 drug is peptide based medicine, which is obtained via the upstream chemical synthesis or biological fermentation. The latter mainly relies on expression in E.coli, yeast and CHO, which leads to the fusion expression between peptides and tags, enjoying higher safety, lower cost and larger production scale. However, peptides obtained by this method possess higher complexity in components, presenting higher requirements for downstream processing players.

Downstream purification process

Downstream chromatography processing differs dramatically in capture stage based on diverse biological fermentation methods used.

GLP-1RA peptides

The purification of normal GLP-1RA peptides can be achieved by using anion exchange chromatography resin in initial purification, removing amino-acid-insufficient impurities and plenty of HCP and HCD before using reversed phase chromatography resin in polishing stage, to remove isomers, degradable peptides and other by-products.

Fc infusion protein GLP-1RA peptides

This type of GLP-1RA peptide possesses certain property of antibody, including high Mol.wt and easy formation of aggregates. Thus, purification can be obtained by capture of Fc infusion protein with Protein A or Protein G affinity resins before further purification step via IEX and HIC resins.

His tagged fusion protein GLP-1RA peptide

Bestchrom Ni pre-packed columns can capture His tagged fusion proteins. When urea, GuHCl or reducing agents are required for dissolving of inclusion bodies, Ni⁺ chelating resins via TED complexation are recommended. Following step shall include polishing step by using IEX, HIC and RPC resins, to improve purity of active peptides.

HAS fusion protein GLP-1RA peptide

Mol.wt of GLP-1RA peptides will increase after being modified by human serum albumin (HAS) while prolonging half-life period. It is recommended to use Bestchrom Blue Bestarose FF resin for the capture of albumin fusion proteins in the initial purification stage.

Conclusion

Biological activity of GLP-1 drugs GLP-1 will be largely influenced by the purity of GLP-1. Different purification scheme shall be adopted based on specific project strategy, indicating the crucial role it plays in the boost of product quality.

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