Site-Specific Lipidation of a Small-Sized Protein Binder Enhances the Antitumor Activity through Extended Blood Half-Life

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dc.contributor.authorKim, Tae Yoonko
dc.contributor.authorNam, You Reeko
dc.contributor.authorPark, Jin Hoko
dc.contributor.authorLee, Dong-Eunko
dc.contributor.authorKim, Hak-Sungko
dc.date.accessioned2020-09-22T08:55:13Z-
dc.date.available2020-09-22T08:55:13Z-
dc.date.created2020-09-14-
dc.date.issued2020-08-
dc.identifier.citationACS OMEGA, v.5, no.31, pp.19778 - 19784-
dc.identifier.issn2470-1343-
dc.identifier.urihttp://hdl.handle.net/10203/276396-
dc.description.abstractProtein 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.languageEnglish-
dc.publisherAMER CHEMICAL SOC-
dc.titleSite-Specific Lipidation of a Small-Sized Protein Binder Enhances the Antitumor Activity through Extended Blood Half-Life-
dc.typeArticle-
dc.identifier.wosid000562138900049-
dc.identifier.scopusid2-s2.0-85089518539-
dc.type.rimsART-
dc.citation.volume5-
dc.citation.issue31-
dc.citation.beginningpage19778-
dc.citation.endingpage19784-
dc.citation.publicationnameACS OMEGA-
dc.identifier.doi10.1021/acsomega.0c02555-
dc.contributor.localauthorKim, Hak-Sung-
dc.contributor.nonIdAuthorNam, You Ree-
dc.contributor.nonIdAuthorPark, Jin Ho-
dc.contributor.nonIdAuthorLee, Dong-Eun-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusFATTY-ACID-BINDING-
dc.subject.keywordPlusNEONATAL FC-RECEPTOR-
dc.subject.keywordPlusFUSION PROTEINS-
dc.subject.keywordPlusPHARMACOKINETICS-
dc.subject.keywordPlusINFLAMMATION-
dc.subject.keywordPlusALBUMIN-
dc.subject.keywordPlusPEGYLATION-
dc.subject.keywordPlusSTRATEGIES-
dc.subject.keywordPlusMOLECULES-
dc.subject.keywordPlusEXTENSION-

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