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Stabilizing Peptide Fusion for Solving the Stability and Solubility Problems of Therapeutic Proteins

 Eui Nam Lee  ;  Young Mok Kim  ;  Hye Ja Lee  ;  Sang Woo Park  ;  Han Young Jung  ;  Jae Myun Lee  ;  Yong-Ho Ahn  ;  Jongsun Kim 
 PHARMACEUTICAL RESEARCH, Vol.22(10) : 1735-1746, 2005 
Journal Title
Issue Date
Animals ; Drug Stability ; Drug Storage ; Granulocyte Colony-Stimulating Factor/chemistry ; Granulocyte Colony-Stimulating Factor/genetics ; Granulocyte Colony-Stimulating Factor/pharmacokinetics ; Hot Temperature ; Human Growth Hormone/chemistry ; Human Growth Hormone/genetics ; Human Growth Hormone/pharmacokinetics ; Humans ; Male ; Peptides/chemistry* ; Proteins/chemistry* ; Proteins/genetics ; Proteins/pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins/chemistry* ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/pharmacokinetics ; Solubility ; alpha-Synuclein/chemistry* ; alpha-Synuclein/genetics
Protein aggregation ; protein solubility ; protein stability ; stabilizing peptide ; therapeutic proteins
PURPOSE: Protein aggregation is a major stability problem of therapeutic proteins. We investigated whether a novel stabilizing peptide [acidic tail of synuclein (ATS) peptide] could be generally used to make a more stable and soluble form of therapeutic proteins, particularly those having solubility or aggregation problems. METHODS: We produced ATS fusion proteins by fusing the stabilizing peptide to three representative therapeutic proteins, and then compared the stress-induced aggregation profiles, thermostability, and solubility of them. We also compared the in vivo stability of these ATS fusion proteins by studying their pharmacokinetics in rats. RESULTS: The human growth hormone-ATS (hGH-ATS) and granulocyte colony-stimulating factor-ATS (G-CSF-ATS) fusion proteins were fully functional as determined by cell proliferation assay, and the ATS fusion proteins seemed to be very resistant to agitation, freeze/thaw, and heat stresses. The introduction of the ATS peptide significantly increased the storage and thermal stabilities of hGH and G-CSF. The human leptin-ATS fusion protein also seemed to be very resistant to aggregation induced by agitation, freeze/thaw, and heat stresses. Furthermore, the ATS peptide greatly increased the solubility of the fusion proteins. Finally, pharmacokinetic studies in rats revealed that the ATS fusion proteins are also more stable in vivo. CONCLUSION: Our data demonstrate that a more stable and soluble form of therapeutic proteins can be produced by fusing the ATS peptide.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Sun(김종선) ORCID logo https://orcid.org/0000-0002-3149-669X
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Lee, Jae Myun(이재면) ORCID logo https://orcid.org/0000-0002-5273-3113
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