(壹)探討小分子結構與加速胰島類澱粉蛋白聚集功能 (貳)探討乙醯化反應對αA-水晶體蛋白片段(66-80)聚集的影響 (I) Exploring the structure of small molecules to accelerate human islet amyloid polypeptide aggregation (II) Exploring the effect of acetylation on the aggregation of αA-crystallin 66-80

dc.contributor 杜玲嫻 zh_TW
dc.contributor Tu, Ling-Hsien en_US
dc.contributor.author 鄭幃銜 zh_TW
dc.contributor.author Teh, Wei-Xuan en_US
dc.date.accessioned 2020-10-19T06:51:12Z
dc.date.available 不公開
dc.date.available 2020-10-19T06:51:12Z
dc.date.issued 2019
dc.description.abstract 本論文主要分成兩個部分,摘要如下: 第一部分旨在開發尋找可以加速類澱粉蛋白聚集的小分子。在本研究中,我們發現胡椒鹼的衍生物有加速聚胰島類澱粉蛋白聚集的效果。我們利用硫磺素-T動力學實驗對7個胡椒鹼衍生物包含胡椒鹼進行初步的篩檢發現具有胡椒鹼上的苯環以及羧酸這樣的結構都有加速胰島類澱粉蛋白聚集的效果。此外,連接苯環以及羧酸的長度也會影響加速聚集的效果。我們也透過變異胰島類澱粉蛋白上特定位置的胺基酸發現,羧酸會與1號位的賴胺酸以及11號位的精胺酸有靜電作用力而使這類的結構能加速胰島類澱粉蛋白的聚集。 第二部分旨在探討轉譯後修飾對類澱粉蛋白的聚集是否有影響。在本研究中我們探討了乙醯化反應,其中一種轉譯後修飾,對αA水晶體蛋白片段66-80聚集形成類澱粉蛋白纖維是否有影響。我們利用硫磺素-T動力學實驗發現乙醯化後的αA水晶體蛋白片段66-80不會聚集形成類澱粉蛋白纖維。透過穿透式電子顯微鏡的觀察,我們也沒有觀察到乙醯化後的αA水晶體蛋白片段66-80形成典型的類澱粉蛋白纖維。 zh_TW
dc.description.abstract The dissertation is devided into two section, they are as follows: I.Nowaday, scientist turns their focuses on developing small organic compounds that can promote amyloid fibril formation in order to reduce the time in the oligomer state, this process might reduce toxicity that induces by amyloid protein.Here, we found that piperine derivative can induce IAPP aggregation. In this research, we used thioflavin-T kinetic assay to conduct a preliminary screening of 7 piperine derivatives that contain piperine. We found that the structure of benzene and carboxylic acid on piperine can accelerate the formation of IAPP aggregates. We also mutant specific position of IAPP and found that the carboxylic acid might have electrostatic interaction with lysine 1 and arginine 11, thus both structures might allow accelerating the aggregation of IAPP. II.In the second work, we investigate the effect of acetylation, one of post-translational modification, to αA66-80 forming amyloid fibrils. In our thioflavin-T kinetic studies, we found that acetylated αA66-80 peptide loss the ability to form amyloid fibrils. Using transmission electron microscopy, we did not observe acetylated αA66-80 form typical amyloid fibrils. en_US
dc.description.sponsorship 化學系 zh_TW
dc.identifier G060742041S
dc.identifier.uri http://etds.lib.ntnu.edu.tw/cgi-bin/gs32/gsweb.cgi?o=dstdcdr&s=id=%22G060742041S%22.&%22.id.&
dc.identifier.uri http://rportal.lib.ntnu.edu.tw:80/handle/20.500.12235/111149
dc.language 中文
dc.subject 胰島類澱粉蛋白 zh_TW
dc.subject 胡椒鹼衍生物 zh_TW
dc.subject 加速聚集 zh_TW
dc.subject 水晶體蛋白 zh_TW
dc.subject αA水晶體蛋白片段66-80 zh_TW
dc.subject 白內障 zh_TW
dc.subject 乙醯化 zh_TW
dc.subject Islet amyloid polypeptide en_US
dc.subject piperine derivatives en_US
dc.subject accelerate aggregation en_US
dc.subject Crystallin en_US
dc.subject αA66-80 en_US
dc.subject cataract en_US
dc.subject acetylation en_US
dc.title (壹)探討小分子結構與加速胰島類澱粉蛋白聚集功能 (貳)探討乙醯化反應對αA-水晶體蛋白片段(66-80)聚集的影響 zh_TW
dc.title (I) Exploring the structure of small molecules to accelerate human islet amyloid polypeptide aggregation (II) Exploring the effect of acetylation on the aggregation of αA-crystallin 66-80 en_US
Files
Collections