| Preparation and characterization of a novel exendin-4 human serum albumin fusion protein expressed in Pichia pastoris. | |
| | |
MedLine Citation:
|
PMID: 17994612 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
A novel recombinant exendin-4 human serum albumin fusion protein (rEx-4/HSA) expressed in Pichia pastoris was prepared and characterized. Ex-4 is a 39-amino acid peptide isolated from the salivary gland of the lizard Heloderma suspectum and is thought to be a novel therapeutic agent for type 2 diabetes. But to gain a continued effect, the peptide has to be injected twice a day owing to its short plasma half-life (t(1/2) = 2.4 h). To extend the half-life of Ex-4 molecule in vivo, we designed a genetically engineered Ex-4/HSA fusion protein. Between Ex-4 and HSA, a peptide linker GGGGS was inserted and the fusion protein was expressed in methylotrophic yeast P. pastoris with native HSA secretion signal sequence. The recombinant protein was secreted correctly and was obtained with high purity (typically > 98%) by a three-step purification procedure. cAMP assay demonstrated that the fusion protein had a bioactivity similar to Ex-4 for interaction with GLP-1 receptors in vitro. Results from oral glucose tolerance test indicated that rEx-4/HSA could effectively improve glucose tolerance in diabetic db/db mice. Pharmacokinetics studies in cynomologus monkeys also showed that rEx-4/HSA had a much longer plasma half-life. Therefore, rEx-4/HSA fusion protein could potentially be used as a new recombinant biodrug for type 2 diabetes therapy. |
| | |
Authors:
|
Yan-Shan Huang; Zhi Chen; Yi-Qiong Chen; Guo-Chang Ma; Jian-Feng Shan; Wei Liu; Lin-Fu Zhou |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Journal of peptide science : an official publication of the European Peptide Society Volume: 14 ISSN: 1075-2617 ISO Abbreviation: J. Pept. Sci. Publication Date: 2008 May |
Date Detail:
|
Created Date: 2008-04-23 Completed Date: 2008-08-01 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9506309 Medline TA: J Pept Sci Country: England |
Other Details:
|
Languages: eng Pagination: 588-95 Citation Subset: IM |
Affiliation:
|
Department of Cell Biology, School of Medicine, Zhejiang University, Hangzhou, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Base Sequence Blood Glucose / metabolism Cell Line Cricetinae Cyclic AMP / biosynthesis DNA Primers / genetics Female Glucose Tolerance Test Humans Hypoglycemic Agents / isolation & purification, pharmacokinetics, pharmacology Lizards / genetics Mice Mice, Inbred C57BL Peptides / genetics*, isolation & purification*, pharmacokinetics, pharmacology Pichia / genetics Recombinant Fusion Proteins / genetics, isolation & purification, pharmacokinetics, pharmacology Serum Albumin / genetics*, isolation & purification*, pharmacokinetics, pharmacology Transfection Venoms / genetics*, isolation & purification*, pharmacokinetics, pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/Blood Glucose; 0/DNA Primers; 0/Hypoglycemic Agents; 0/Peptides; 0/Recombinant Fusion Proteins; 0/Serum Albumin; 0/Venoms; 141732-76-5/exenatide; 60-92-4/Cyclic AMP |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The minimal fusion peptide of simian immunodeficiency virus corresponds to the 11 first residues of ...
Next Document: Utility of microsatellite analysis in evaluation of pregnancies with placental mesenchymal dysplasia...