Preparation and Evaluation of a 4-Branched Polyethylene Glycol Derivative Modified with Exendin-4 and Stearylamine for Extended Hypoglycemic Action
DC Field | Value | Language |
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dc.contributor.author | Insoo Kim | - |
dc.contributor.author | Kyungwan Ma | - |
dc.contributor.author | Sungho Bae | - |
dc.contributor.author | 윤정현 | - |
dc.contributor.author | 오경택 | - |
dc.contributor.author | 이은성 | - |
dc.contributor.author | 이돈행 | - |
dc.contributor.author | Kang Choon Lee | - |
dc.contributor.author | 윤유석 | - |
dc.date.available | 2019-08-19T06:05:03Z | - |
dc.date.issued | 2010 | - |
dc.identifier.issn | 2093-5552 | - |
dc.identifier.issn | 2093-6214 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/34348 | - |
dc.description.abstract | Albumin-modification has been viewed as one of the most effective ways of extending the short in vivo lifetimes of peptide drugs by delaying glomerular filtration. In this study, we describe a new type 2 anti-diabetic exendin-4 (Ex4) peptide derivative with significant binding ability to human serum albumin (HSA). This exendin-4 derivative consists of a 4-branched polyethylene glycol (PEG)5k (Mw: 20 kDa) modified with three stearylamines (C18-NH2) and one exendin-4 on its branches. PEG and stearylamine were selected to provide functionality to increase molecular size and bind to albumin, respectively. This derivative (3C18-4PEG5k-Ex4) was shown to have larger molecular size (Ca. 152 kDa) than actual (25.0 kDa) when subjected to size-exclusion chromatography, and the fluorescein-tagged 3C18-4PEG5k-Ex4 displayed significant binding to the HSA-immobilized Sepharose CL-4B resin using confocal laser scanning microscopy. Furthermore, 3C18-4PEG5k-Ex4 was found to have acceptable anti-hyperglycemic efficacy via three consecutive oral glucose tolerance testings (OGTT) in fasted type 2 diabetic db/db mice. The HDtotal value (57.6±12.3%) of 3C18-4PEG5k-Ex4 at a 50 nmol/kg dose was 2-fold greater than that (31.0±8.7%) of native exendin-4 in non-fasted db/db mice. Especially, the blood glucose levels in the mice group treated with 3C18-4PEG5k-Ex4 did not rebound to ~150 mg/dL until 24 h after the injection, which obviously shows the extended hypoglycemia. We believe that this derivative has great pharmaceutical potential as a novel long-acting type 2 anti-diabetic injection treatment. | - |
dc.format.extent | 6 | - |
dc.publisher | 한국약제학회 | - |
dc.title | Preparation and Evaluation of a 4-Branched Polyethylene Glycol Derivative Modified with Exendin-4 and Stearylamine for Extended Hypoglycemic Action | - |
dc.type | Article | - |
dc.identifier.bibliographicCitation | Journal of Pharmaceutical Investigation, v.40, no.3, pp 175 - 180 | - |
dc.identifier.kciid | ART001451188 | - |
dc.description.isOpenAccess | N | - |
dc.citation.endPage | 180 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 175 | - |
dc.citation.title | Journal of Pharmaceutical Investigation | - |
dc.citation.volume | 40 | - |
dc.publisher.location | 대한민국 | - |
dc.subject.keywordAuthor | Exendin-4 | - |
dc.subject.keywordAuthor | 4-arm PEG | - |
dc.subject.keywordAuthor | albumin-binding | - |
dc.subject.keywordAuthor | PEG | - |
dc.subject.keywordAuthor | type 2 diabetes | - |
dc.description.journalRegisteredClass | kci | - |
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