DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Tae Yoon | ko |
dc.contributor.author | Seo, Hyo Deok | ko |
dc.contributor.author | Lee, Joong-jae | ko |
dc.contributor.author | Kang, Jung Ae | ko |
dc.contributor.author | Kim, Woo Sik | ko |
dc.contributor.author | Kim, Hye-Min | ko |
dc.contributor.author | Song, Ha-Yeon | ko |
dc.contributor.author | Park, Ji Min | ko |
dc.contributor.author | Lee, Dong-Eun | ko |
dc.contributor.author | Kim, Hak-Sung | ko |
dc.date.accessioned | 2018-07-24T02:22:09Z | - |
dc.date.available | 2018-07-24T02:22:09Z | - |
dc.date.created | 2018-07-04 | - |
dc.date.created | 2018-07-04 | - |
dc.date.created | 2018-07-04 | - |
dc.date.created | 2018-07-04 | - |
dc.date.created | 2018-07-04 | - |
dc.date.issued | 2018-06 | - |
dc.identifier.citation | JOURNAL OF CONTROLLED RELEASE, v.279, pp.282 - 291 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | http://hdl.handle.net/10203/244014 | - |
dc.description.abstract | Small-sized non-antibody scaffolds have attracted considerable interest as alternatives to immunoglobulin antibodies. However, their short half-life is considered a drawback in the development of therapeutic agents. Here we demonstrate that a homo-dimeric form of a repebody enhances the anti-tumor activity than a monomeric form through prolonged blood circulation. Spytag and spycatcher were genetically fused to the C-terminus of a respective human IL-6-specific repebody, and the resulting two repebody constructs were mixed at an equimolar ratio to produce a homo-dimeric form through interaction between spytag and spycatcher. The homo-dimeric repebody was detected as a single band in the SDS-PAGE analysis with an expected molecular size (78 kDa), showing high stability and homogeneity. The dimeric repebody was shown to simultaneously accommodate two hIL-6 molecules, and its binding affinity for hIL-6 was estimated to be comparable to a monomeric repebody. The serum concentration of the dimeric repebody was observed to be about 5.5 times higher than a monomeric repebody, consequently leading to considerably higher tumor suppression effect in human tumor xenograft mice. The present approach can be effectively used for prolonging the blood half-life of small-sized protein binders, resulting in enhanced therapeutic efficacy. | - |
dc.language | English | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.title | A dimeric form of a small-sized protein binder exhibits enhanced anti-tumor activity through prolonged blood circulation | - |
dc.type | Article | - |
dc.identifier.wosid | 000433211300026 | - |
dc.identifier.scopusid | 2-s2.0-85046160855 | - |
dc.type.rims | ART | - |
dc.citation.volume | 279 | - |
dc.citation.beginningpage | 282 | - |
dc.citation.endingpage | 291 | - |
dc.citation.publicationname | JOURNAL OF CONTROLLED RELEASE | - |
dc.identifier.doi | 10.1016/j.jconrel.2018.04.039 | - |
dc.contributor.localauthor | Kim, Hak-Sung | - |
dc.contributor.nonIdAuthor | Lee, Joong-jae | - |
dc.contributor.nonIdAuthor | Kang, Jung Ae | - |
dc.contributor.nonIdAuthor | Kim, Woo Sik | - |
dc.contributor.nonIdAuthor | Kim, Hye-Min | - |
dc.contributor.nonIdAuthor | Song, Ha-Yeon | - |
dc.contributor.nonIdAuthor | Park, Ji Min | - |
dc.contributor.nonIdAuthor | Lee, Dong-Eun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Repebody | - |
dc.subject.keywordAuthor | Homo-dimer | - |
dc.subject.keywordAuthor | Blood circulation time | - |
dc.subject.keywordAuthor | Spytag-spycatcher | - |
dc.subject.keywordAuthor | Therapeutic efficacy | - |
dc.subject.keywordPlus | FC-FUSION PROTEINS | - |
dc.subject.keywordPlus | BINDING-PROTEINS | - |
dc.subject.keywordPlus | HALF-LIFE | - |
dc.subject.keywordPlus | THERAPEUTIC PROTEINS | - |
dc.subject.keywordPlus | ALBUMIN-BINDING | - |
dc.subject.keywordPlus | SCAFFOLDS | - |
dc.subject.keywordPlus | ANTIBODIES | - |
dc.subject.keywordPlus | AFFINITY | - |
dc.subject.keywordPlus | PEGYLATION | - |
dc.subject.keywordPlus | STRATEGY | - |
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