US EPA

1043501 

Journal Article 

Preparation and PEGylation of exendin-4 peptide secreted from yeast Pichia pastoris 

Zhou, J; Cai, ZH; Li, L; Kou, C; Gao, YF 

In Press 

1 

European Journal of Pharmaceutics and Biopharmaceutics
ISSN: 0939-6411
EISSN: 1873-3441 

English 

19602371 

10.1016/j.ejpb.2009.02.001 

http://linkinghub.elsevier.com/retrieve/pii/S0939641109000447
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Exendin-4, a peptide analogue of glucagon-like peptide (GLP-1), has been developed for treatment of type 2 diabetes. Herein, the secretive exendin-4 peptide, expressed by methanol induction in Pichia pastoris, was purified to near homogeneity by Ni-NTA agarose chromatography. 103.6 mg of protein was obtained from 1 L of the supernatant and its purity was 96.1%. Subsequently, the PEGylated exendin-4 was prepared. The bioactivity of exendin-4 was determined by examining the glucose-lowering and insulin-releasing ability in plasma. Then, a safety evaluation was performed by histological examination of the main organs (liver, kidney and pancreas). PEGylated exendin-4 displayed glucose-lowering and insulin-stimulating action in vivo without obvious damage to the above organs. The results suggest that the P. pastoris expression could be used to produce large quantities of exendin-4 and PEGylation is a useful tool to maintain and enhance bioactivity of the peptide.