DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Daejin | ko |
dc.contributor.author | Jeon, Hyungsu | ko |
dc.contributor.author | Ahn, Sukyung | ko |
dc.contributor.author | Choi, Won Il | ko |
dc.contributor.author | Kim, Sunghyun | ko |
dc.contributor.author | Jon, Sangyong | ko |
dc.date.accessioned | 2017-08-08T06:06:27Z | - |
dc.date.available | 2017-08-08T06:06:27Z | - |
dc.date.created | 2017-07-17 | - |
dc.date.created | 2017-07-17 | - |
dc.date.issued | 2017-06 | - |
dc.identifier.citation | JOURNAL OF CONTROLLED RELEASE, v.256, pp.114 - 120 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.uri | http://hdl.handle.net/10203/225098 | - |
dc.description.abstract | Although the peptide, exenatide, has been widely used as a drug for the treatment of type 2 diabetes, its short plasma half-life requires frequent subcutaneous injection, resulting in poor patient compliance in addition to side effects such as infection at the sites of injection. Here, we report a novel long-acting fusion peptide comprising exenatide and a human serum albumin (HSA)-binding aptide. A phage display screen of a library of aptides, yielded an HSA-specific aptide (APT(HSA)) that bound HSA with a K-d of 188 nM. The recombinant fusion peptide comprising exenatide and APT(HSA) (exenatide-APT(HSA)) was expressed in Escherichia coli and purified by affinity and size-exclusion chromatography. The resulting exenatide-APTHSA fusion peptide showed glucose-induced insulin secretion activity similar to that of native exenatide when tested in vitro using the INS-1 cell line. A pharmacokinetic analysis of exenatide-APT(HSA) after subcutaneous administration revealed a 4-fold longer plasma half-life (1.3 vs. 0.35 h) compared with exenatide. Furthermore, exenatide-APT(HSA) showed significantly improved anti-hyperglycemic effects in oral glucose tolerance tests and enhanced hypoglycemic effects compared with exenatide in a db/db type 2 diabetes mouse model. These results suggest that the exenatide-APT(HSA) fusion peptide could be used as a potential anti-diabetic agent for the treatment of type 2 diabetes. | - |
dc.language | English | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.subject | SITE-SPECIFIC PEGYLATION | - |
dc.subject | GLUCAGON-LIKE PEPTIDE-1 | - |
dc.subject | POLYETHYLENE-GLYCOL | - |
dc.subject | RECEPTOR AGONIST | - |
dc.subject | MOUSE MODELS | - |
dc.subject | HEPATITIS-C | - |
dc.subject | EXENATIDE | - |
dc.subject | EXENDIN-4 | - |
dc.subject | PROTEIN | - |
dc.subject | PHARMACOKINETICS | - |
dc.title | An approach for half-life extension and activity preservation of an anti-diabetic peptide drug based on genetic fusion with an albumin-binding aptide | - |
dc.type | Article | - |
dc.identifier.wosid | 000403324800011 | - |
dc.identifier.scopusid | 2-s2.0-85018951130 | - |
dc.type.rims | ART | - |
dc.citation.volume | 256 | - |
dc.citation.beginningpage | 114 | - |
dc.citation.endingpage | 120 | - |
dc.citation.publicationname | JOURNAL OF CONTROLLED RELEASE | - |
dc.identifier.doi | 10.1016/j.jconrel.2017.04.036 | - |
dc.contributor.localauthor | Jon, Sangyong | - |
dc.contributor.nonIdAuthor | Choi, Won Il | - |
dc.contributor.nonIdAuthor | Kim, Sunghyun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Aptides | - |
dc.subject.keywordAuthor | Exenatide | - |
dc.subject.keywordAuthor | Human serum albumin | - |
dc.subject.keywordAuthor | Fusion peptide | - |
dc.subject.keywordAuthor | GLP-1 | - |
dc.subject.keywordAuthor | Type 2 diabetes | - |
dc.subject.keywordPlus | SITE-SPECIFIC PEGYLATION | - |
dc.subject.keywordPlus | GLUCAGON-LIKE PEPTIDE-1 | - |
dc.subject.keywordPlus | POLYETHYLENE-GLYCOL | - |
dc.subject.keywordPlus | RECEPTOR AGONIST | - |
dc.subject.keywordPlus | MOUSE MODELS | - |
dc.subject.keywordPlus | HEPATITIS-C | - |
dc.subject.keywordPlus | EXENATIDE | - |
dc.subject.keywordPlus | EXENDIN-4 | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | PHARMACOKINETICS | - |
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