DC Field | Value | Language |
---|---|---|
dc.contributor.author | Se Jin Lim | - |
dc.contributor.author | Yang, SI | - |
dc.contributor.author | Yang, SH | - |
dc.contributor.author | Choi, DH | - |
dc.contributor.author | Choi, SY | - |
dc.contributor.author | Kim, HS | - |
dc.contributor.author | Jang, DS | - |
dc.contributor.author | Jin, KS | - |
dc.contributor.author | Chung, YK | - |
dc.contributor.author | Kim, SH | - |
dc.contributor.author | Paik, SH | - |
dc.contributor.author | Park, YC | - |
dc.contributor.author | Chung, MK | - |
dc.contributor.author | Kim, YB | - |
dc.contributor.author | Han, KH | - |
dc.contributor.author | Choi, KY | - |
dc.contributor.author | Sung, YC | - |
dc.date.accessioned | 2016-03-31T09:07:29Z | - |
dc.date.available | 2016-03-31T09:07:29Z | - |
dc.date.created | 2012-03-22 | - |
dc.date.issued | 2011-09-16 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.other | 2011-OAK-0000025082 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/16674 | - |
dc.description.abstract | Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody-and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc retained "Y-shaped" structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to Fc gamma R I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUC(last)). Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach. | - |
dc.description.statementofresponsibility | X | - |
dc.language | English | - |
dc.publisher | Public Library of Science | - |
dc.relation.isPartOf | PLOS ONE | - |
dc.subject | RECOMBINANT-HUMAN-ERYTHROPOIETIN | - |
dc.subject | STIMULATING PROTEIN NESP | - |
dc.subject | I-RELATED RECEPTOR | - |
dc.subject | BIOLOGICAL-ACTIVITY | - |
dc.subject | BINDING-SITE | - |
dc.subject | HUMAN-IGG | - |
dc.subject | ANTIBODIES | - |
dc.subject | PHARMACOKINETICS | - |
dc.subject | CELLS | - |
dc.subject | PHARMACODYNAMICS | - |
dc.title | Natural Form of Noncytolytic Flexible Human Fc as a Long-Acting Carrier of Agonistic Ligand, Erythropoietin | - |
dc.type | Article | - |
dc.contributor.college | 생명과학과 | - |
dc.identifier.doi | 10.1371/JOURNAL.PONE.0024574 | - |
dc.author.google | Im, SJ | - |
dc.author.google | Yang, SI | - |
dc.author.google | Yang, SH | - |
dc.author.google | Choi, DH | - |
dc.author.google | Choi, SY | - |
dc.author.google | Kim, HS | - |
dc.author.google | Jang, DS | - |
dc.author.google | Jin, KS | - |
dc.author.google | Chung, YK | - |
dc.author.google | Kim, SH | - |
dc.author.google | Paik, SH | - |
dc.author.google | Park, YC | - |
dc.author.google | Chung, MK | - |
dc.author.google | Kim, YB | - |
dc.author.google | Han, KH | - |
dc.author.google | Choi, KY | - |
dc.author.google | Sung, YC | - |
dc.relation.volume | 6 | - |
dc.relation.issue | 9 | - |
dc.relation.startpage | E24574 | - |
dc.relation.lastpage | E24574 | - |
dc.contributor.id | 10052985 | - |
dc.relation.journal | PLOS ONE | - |
dc.relation.index | SCI급, SCOPUS 등재논문 | - |
dc.relation.sci | SCI | - |
dc.collections.name | Journal Papers | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | PLOS ONE, v.6, no.9, pp.E24574 - E24574 | - |
dc.identifier.wosid | 000295173800027 | - |
dc.date.tcdate | 2019-01-01 | - |
dc.citation.endPage | E24574 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | E24574 | - |
dc.citation.title | PLOS ONE | - |
dc.citation.volume | 6 | - |
dc.contributor.affiliatedAuthor | Choi, KY | - |
dc.contributor.affiliatedAuthor | Sung, YC | - |
dc.identifier.scopusid | 2-s2.0-80052823581 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.wostc | 30 | - |
dc.description.scptc | 20 | * |
dc.date.scptcdate | 2018-05-121 | * |
dc.type.docType | Article | - |
dc.subject.keywordPlus | I-RELATED RECEPTOR | - |
dc.subject.keywordPlus | BIOLOGICAL-ACTIVITY | - |
dc.subject.keywordPlus | HUMAN-IGG | - |
dc.subject.keywordPlus | PHARMACOKINETICS | - |
dc.subject.keywordPlus | ANTIBODIES | - |
dc.subject.keywordPlus | FLEXIBILITY | - |
dc.subject.keywordPlus | MATURATION | - |
dc.subject.keywordPlus | INHIBITOR | - |
dc.subject.keywordPlus | DESIGN | - |
dc.subject.keywordPlus | ALPHA | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
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