DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Tae Yoon | ko |
dc.contributor.author | Nam, You Ree | ko |
dc.contributor.author | Park, Jin Ho | ko |
dc.contributor.author | Lee, Dong-Eun | ko |
dc.contributor.author | Kim, Hak-Sung | ko |
dc.date.accessioned | 2020-09-22T08:55:13Z | - |
dc.date.available | 2020-09-22T08:55:13Z | - |
dc.date.created | 2020-09-14 | - |
dc.date.issued | 2020-08 | - |
dc.identifier.citation | ACS OMEGA, v.5, no.31, pp.19778 - 19784 | - |
dc.identifier.issn | 2470-1343 | - |
dc.identifier.uri | http://hdl.handle.net/10203/276396 | - |
dc.description.abstract | Protein and peptide therapeutics tend to have a short blood circulation time mainly caused by rapid clearance in kidney, leading to a low therapeutic efficacy. Here, we demonstrate that the antitumor activity of a small-sized protein binder can be significantly enhanced by prolonged blood half-life through site-specific lipidation. An unnatural amino acid was genetically incorporated into a specific site with the highest accessibility in a human interleukin-6 (IL-6)-targeting protein binder with a size of 30.8 kDa, followed by conjugation with palmitic acid using cooper-free click chemistry. The resulting protein binder was shown to have a binding capacity for serum albumin, maintaining a comparable binding affinity for human IL-6 to the native protein binder. The terminal half-life of the lipidated protein binder was estimated to be 10.7 h, whereas the native one had a half-life of 20 min, resulting in a significantly enhanced tumor suppression effect. The present approach can be generally applied to small-sized therapeutic proteins for the elongation of circulation time and increase of bioavailability in blood, consequently enhancing their therapeutic efficacy. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Site-Specific Lipidation of a Small-Sized Protein Binder Enhances the Antitumor Activity through Extended Blood Half-Life | - |
dc.type | Article | - |
dc.identifier.wosid | 000562138900049 | - |
dc.identifier.scopusid | 2-s2.0-85089518539 | - |
dc.type.rims | ART | - |
dc.citation.volume | 5 | - |
dc.citation.issue | 31 | - |
dc.citation.beginningpage | 19778 | - |
dc.citation.endingpage | 19784 | - |
dc.citation.publicationname | ACS OMEGA | - |
dc.identifier.doi | 10.1021/acsomega.0c02555 | - |
dc.contributor.localauthor | Kim, Hak-Sung | - |
dc.contributor.nonIdAuthor | Nam, You Ree | - |
dc.contributor.nonIdAuthor | Park, Jin Ho | - |
dc.contributor.nonIdAuthor | Lee, Dong-Eun | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | FATTY-ACID-BINDING | - |
dc.subject.keywordPlus | NEONATAL FC-RECEPTOR | - |
dc.subject.keywordPlus | FUSION PROTEINS | - |
dc.subject.keywordPlus | PHARMACOKINETICS | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | ALBUMIN | - |
dc.subject.keywordPlus | PEGYLATION | - |
dc.subject.keywordPlus | STRATEGIES | - |
dc.subject.keywordPlus | MOLECULES | - |
dc.subject.keywordPlus | EXTENSION | - |
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