| DC 欄位 |
值 |
語言 |
| DC.contributor | 化學學系 | zh_TW |
| DC.creator | 鄭仁華 | zh_TW |
| DC.creator | Ren-Hua Jheng | en_US |
| dc.date.accessioned | 2021-9-1T07:39:07Z | |
| dc.date.available | 2021-9-1T07:39:07Z | |
| dc.date.issued | 2021 | |
| dc.identifier.uri | http://ir.lib.ncu.edu.tw:88/thesis/view_etd.asp?URN=107223007 | |
| dc.contributor.department | 化學學系 | zh_TW |
| DC.description | 國立中央大學 | zh_TW |
| DC.description | National Central University | en_US |
| dc.description.abstract | 穀胱甘肽是生物體內一種相當重要的小分子硫醇，其能扮演抗氧化劑來調節細胞的氧化還原壓力之外，同時也參與多項的生理代謝反應。再者，由於大部分腫瘤組織中穀胱甘肽的濃度皆為正常組織的數倍，此濃度的差異對於治療癌症的奈米載體而言，被視為一個良好的引信訊號來促使藥物釋放。過去有許多以穀胱甘肽為引信的微脂體藥物陸續被開發，其中大多數的研究皆以利用具有還原應答能力的非天然性磷脂質來作為微脂體的主要脂質組成，但此種磷脂質可能造成生物相容性上的相關疑慮。在本研究中，我們利用自然界的膜活性胜肽為基礎，成功開發了以穀胱甘肽為引信的破膜胜肽，並且此狀態下的破膜活性會被胜肽序列上的遮蔽區塊抑制。由於此多肽有硫醇敏感設計，與傳統多肽與微脂體的硫醇與丁二醯亞胺反應不相容，因此需開發新的多肽與微脂體共軛聯結方式。透過張力促使的疊氮-炔烴的環加成反應，我們成功地將此胜肽修飾於微脂體的表面上，也成功地促使引信穀胱甘肽可以控制微脂體的藥物釋放。從多肽的還原測試實驗中，可以發現此引信響應的胜肽可對於穀胱甘肽具有引信響應的能力，並同時轉變成具有高破膜活性的多肽型式。在藥物釋放方面，引信響應的多肽微脂體與腫瘤濃度下的穀胱甘肽作用後，其會造成較高比例藥物阿黴素的釋放。最後，我們藉由分析胜肽的圓二色光譜，發現此胜肽在與引信作用後，會造成胜肽兩親媒性二級結構上的增加，進而影響微脂體的藥物釋放。 | zh_TW |
| dc.description.abstract | Reduced glutathione (GSH) is an important low-molecular-weight physiological thiol that can be serve as antioxidant for balancing the redox environment of cells and adjusts many significant biological metabolisms. Because of the concentration of glutathione in cancerous tissue is higher than normal level, it can be used as a good triggering signal for nanocarrier to release drug. As a result, a lot of liposomal drugs that can be triggered release by glutathione have been developed in the past decade. However, most liposomes mentioned above are composed of thiol-responsive “unnatural” phospholipids, which have potential safety issue. In this study, we intend to develop a GSH-responsive peptidyl liposome which is more biocompatible. The designed thio-responsive peptide is not compatible with conventional thiol-maleimide chemistry to conjugate onto liposome, and new cross-linking chemistry is needed. We successfully developed peptide-to-liposome conjugation by strain-promote azide-alkyne cycloaddition. We also successfully induce the reductive cleavage of the GSH-responsive peptide on liposome and trigger liposome release. Finally, through the circular dichroism analysis, we discovered the correlation between amphiphilic helicity of liposomal peptide and liposome release. | en_US |
| DC.subject | 穀胱甘肽 | zh_TW |
| DC.subject | 膜活性多肽 | zh_TW |
| DC.subject | 引信釋放 | zh_TW |
| DC.subject | 以穀胱甘肽為引信響應的多肽微脂體 | zh_TW |
| DC.subject | glutathione | en_US |
| DC.subject | membrane active peptide | en_US |
| DC.subject | triggered release | en_US |
| DC.subject | GSH-responsive peptidyl liposome | en_US |
| DC.title | 藉由點擊化學製備穀胱甘肽控制藥物釋放之胜肽微脂體 | zh_TW |
| dc.language.iso | zh-TW | zh-TW |
| DC.title | Using Click Conjugation to Generate Glutathione Responsive Peptidyl Liposome | en_US |
| DC.type | 博碩士論文 | zh_TW |
| DC.type | thesis | en_US |
| DC.publisher | National Central University | en_US |