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

DC FieldValueLanguage
dc.contributor.author김종선-
dc.contributor.author안용호-
dc.contributor.author이재면-
dc.date.accessioned2017-10-26T06:18:25Z-
dc.date.available2017-10-26T06:18:25Z-
dc.date.issued2005-
dc.identifier.issn0724-8741-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/150774-
dc.description.abstractPURPOSE: 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.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherKluwer Academic/Plenum Publishers-
dc.relation.isPartOfPHARMACEUTICAL RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHDrug Stability-
dc.subject.MESHDrug Storage-
dc.subject.MESHGranulocyte Colony-Stimulating Factor/chemistry-
dc.subject.MESHGranulocyte Colony-Stimulating Factor/genetics-
dc.subject.MESHGranulocyte Colony-Stimulating Factor/pharmacokinetics-
dc.subject.MESHHot Temperature-
dc.subject.MESHHuman Growth Hormone/chemistry-
dc.subject.MESHHuman Growth Hormone/genetics-
dc.subject.MESHHuman Growth Hormone/pharmacokinetics-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHPeptides/chemistry*-
dc.subject.MESHProteins/chemistry*-
dc.subject.MESHProteins/genetics-
dc.subject.MESHProteins/pharmacokinetics-
dc.subject.MESHRats-
dc.subject.MESHRats, Sprague-Dawley-
dc.subject.MESHRecombinant Fusion Proteins/chemistry*-
dc.subject.MESHRecombinant Fusion Proteins/genetics-
dc.subject.MESHRecombinant Fusion Proteins/pharmacokinetics-
dc.subject.MESHSolubility-
dc.subject.MESHalpha-Synuclein/chemistry*-
dc.subject.MESHalpha-Synuclein/genetics-
dc.titleStabilizing Peptide Fusion for Solving the Stability and Solubility Problems of Therapeutic Proteins-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Microbiology (미생물학교실)-
dc.contributor.departmentDept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)-
dc.contributor.departmentDept. of Microbiology (미생물학교실)-
dc.contributor.googleauthorEui Nam Lee-
dc.contributor.googleauthorYoung Mok Kim-
dc.contributor.googleauthorHye Ja Lee-
dc.contributor.googleauthorSang Woo Park-
dc.contributor.googleauthorHan Young Jung-
dc.contributor.googleauthorJae Myun Lee-
dc.contributor.googleauthorYong-Ho Ahn-
dc.contributor.googleauthorJongsun Kim-
dc.identifier.doi10.1007/s11095-005-6489-4-
dc.contributor.localIdA00921-
dc.contributor.localIdA02249-
dc.contributor.localIdA03071-
dc.relation.journalcodeJ02503-
dc.identifier.eissn1573-904X-
dc.identifier.pmid16180132-
dc.identifier.urlhttp://link.springer.com/article/10.1007%2Fs11095-005-6489-4-
dc.subject.keywordProtein aggregation-
dc.subject.keywordprotein solubility-
dc.subject.keywordprotein stability-
dc.subject.keywordstabilizing peptide-
dc.subject.keywordtherapeutic proteins-
dc.contributor.alternativeNameKim, Jong Sun-
dc.contributor.alternativeNameAhn, Yong Ho-
dc.contributor.alternativeNameLee, Jae Myun-
dc.citation.volume22-
dc.citation.number10-
dc.citation.startPage1735-
dc.citation.endPage1746-
dc.identifier.bibliographicCitationPHARMACEUTICAL RESEARCH, Vol.22(10) : 1735-1746, 2005-
dc.date.modified2017-05-04-
dc.identifier.rimsid44746-
dc.type.rimsART-
Appears in Collections:
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

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