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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 戴桓青(Hwan-Ching Tai) | |
| dc.contributor.author | Yu-Hsuan Liu | en |
| dc.contributor.author | 劉又瑄 | zh_TW |
| dc.date.accessioned | 2021-06-15T12:50:10Z | - |
| dc.date.available | 2016-08-03 | |
| dc.date.copyright | 2016-08-03 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2016-07-20 | |
| dc.identifier.citation | 1. Grune, T., Shringarpure, R., Sitte, N., and Davies, K. (2001). Age-related changes in protein oxidation and proteolysis in mammalian cells. J. Gerontol. A, Biol. Sci. Med. Sci. 56, 459-467.
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Biomedical Optical Imaging, (New York: Oxford University Press) | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50640 | - |
| dc.description.abstract | 活性氧化物質造成的蛋白質氧化常和老化及神經退化疾病作關聯。蛋白質中，能和金屬離子螯合的組胺酸是常見的氧化傷害標的物。而具有顯著發色特性的色胺酸，可經由光游離作用產生自由基，最後造成氧化傷害。近期研究中發現，2-氧基組胺酸與犬尿胺酸分別是組胺酸和色胺酸主要的氧化產物，並且有潛力作為蛋白質氧化受損的生物標記物。但它們的生物物理及生化特性都尚未被透徹了解。
我們發展了能有效地在合成的多肽上產生2-氧基組胺酸和犬尿胺酸的方法。在二價銅離子/抗壞血酸鈉/氧氣的金屬催化氧化系統中，我們調整了試劑的比例與反應的緩衝溶液系統，使產生2-氧基組胺酸的反應產率較文獻報導增加了十倍以上。而藉由孟加拉玫紅為光敏劑的光氧化反應，含色胺酸的多肽被完全氧化，且主要產物為犬尿胺酸多肽。這些方法讓我們能分離出完全氧化的含2-氧基組胺酸短肽與含犬尿胺酸多肽，以鑑定其性質。 組胺酸被氧化成2-氧基組胺酸的結構轉變，使得其在液相層析法的分析中，在碳-18的管柱的滯留時間較長。然而色胺酸的結構轉變，則帶來相反的變化，滯留時間較原先更短。兩者的結構在電噴灑串聯式質譜實驗中展現高度的穩定性。因此針對2-氧基組胺酸和犬尿胺酸做蛋白質體的質譜分析是可行的，我們氧化方法所合成的2-氧基組胺酸和犬尿胺酸多肽可以作為這類質譜實驗的標準品。 為了瞭解2-氧基組胺酸和犬尿胺酸殘基和其他細胞內因子可能的交互作用，我們將合成的多肽接上螢光染料。利用細胞蛋白質體微陣列晶片 ，和我們合成的探針作用，試圖尋找潛在的結合因子。為了後續蛋白質的修復或降解，細胞內可能會有能夠辨識這些氧化殘基的因子，我們的目標就是鑑定這些細胞因子，試圖了解細胞對蛋白質品質調控的機制。 | zh_TW |
| dc.description.abstract | Protein oxidation by reactive oxygen species has been associated with aging and neurodegenerative disorders. Histidine is a major target for metal-catalyzed oxidation due to its metal chelating property. Tryptophan can undergo photoionization due to its significant chromophoric characteristics, yielding both excited state species and radicals and then resulting in oxidative damage. 2-Oxohistidine and kynurenine, the major products of histidine and tryptophan oxidation, respectively, have been recently identified as markers of oxidative damage in biological systems, but their biophysical and biochemical properties are understudied.
We developed efficient methods to generate 2-oxohistidine and kynurenine side chains, from both monomers and peptides. For 2-oxohistidine, by optimizing reagent ratios and buffering condition in Cu2+/ascorbate/O2 reaction system, we improved the yield more than 10 fold compared to reported conditions. For kynurenine, via Rose Bengal-sensitized photooxidation, the tryptophan-containing peptide is completely oxidized, yielding kynurenine-containing peptide as major product. These methods allowed us to obtain homogeneously modified 2-oxohistidine and kynurenine peptides for further characterization. Conversion of histidine to 2-oxohistidine increased retention time in reverse-phase liquid chromatography; conversion of tryptophan to kynurenine had the opposite effect. Both oxidation products showed general stability in LC-MS/MS experiments as they underwent electrospray ionization and collision-induced dissociation. It should be feasible to analyze 2-oxohistidine-modified and kynurenine-modified proteome in large scale with shotgun protein mass spectrometry. The 2-oxohistidine-containing and kynurenine-containing peptides were conjugated with DyLight fluorophores to make probes for protein microarray analysis against E.coli proteomes. Our goal is to identify cellular proteins that potentially interact with oxidized peptides. These cellular factors may have the potential to recognize oxidized proteins and send them to degradation pathways. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T12:50:10Z (GMT). No. of bitstreams: 1 ntu-104-R02223213-1.pdf: 3604313 bytes, checksum: 32175635ecaf30fb775a6c611f11508f (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 第1章、 緒論 1
1.1 研究目標 1 1.2 活性氧化物種…………….. 1 1.3 蛋白質氧化 3 1.4 老化與疾病的自由基理論 9 1.5 組胺酸的生物功能 10 1.6 組胺酸的金屬催化氧化反應 11 1.7 2-氧基組胺酸的生物研究 13 1.8 色胺酸的生物功能 14 1.9 單線態氧對色胺酸的氧化 16 1.10 犬尿胺酸的生物研究 18 1.11 微陣列蛋白質晶片 20 第2章、 結果與討論 22 2.1 多肽中組胺酸殘基的氧化 22 2.1.1 含組胺酸多肽的序列設計 22 2.1.2 反應條件與液相層析質譜分析 22 2.1.3 利用液相層析串聯式質譜儀鑑定含組胺酸多肽的氧化位置 25 2.2 多肽中色胺酸殘基的氧化 28 2.2.1 含色胺酸多肽的序列設計 28 2.2.2 反應條件與液相層析質譜分析 28 2.2.3 利用液相層析串聯式質譜儀鑑定含色胺酸多肽的氧化位置 34 2.3 以微陣列蛋白質晶片分析氧化多肽探針的互動蛋白質 38 2.3.1 合成多肽螢光探針 38 2.3.2 多肽探針與其互動蛋白質分析 41 第3章、 結論 45 3.1 氧化多肽的合成產率提升 45 3.2 初步的生物發現 45 第4章、 實驗材料與方法 47 4.1 實驗一般說明與儀器裝置 47 4.2 實驗方法 47 4.2.1 含組胺酸多肽的氧化 47 4.2.2 含色胺酸多肽的氧化 48 4.2.3 多肽與DyLight染料的接合 48 4.2.4 以LC-MS/MS鑑定多肽的實驗方法 49 4.2.5 微陣列蛋白質晶片實驗與數據處理 50 附錄 51 參考文獻 57 | |
| dc.language.iso | zh-TW | |
| dc.subject | 活性氧化物質 | zh_TW |
| dc.subject | 犬尿胺酸 | zh_TW |
| dc.subject | 2-氧基組胺酸 | zh_TW |
| dc.subject | 活性氧化物質 | zh_TW |
| dc.subject | 金屬催化氧化 | zh_TW |
| dc.subject | 光游離 | zh_TW |
| dc.subject | 2-氧基組胺酸 | zh_TW |
| dc.subject | 蛋白質微陣列 | zh_TW |
| dc.subject | 蛋白質微陣列 | zh_TW |
| dc.subject | 光游離 | zh_TW |
| dc.subject | 金屬催化氧化 | zh_TW |
| dc.subject | 犬尿胺酸 | zh_TW |
| dc.subject | kynurenine | en |
| dc.subject | 2-oxohistidine | en |
| dc.subject | reactive oxygen species | en |
| dc.subject | metal-catalyzed oxidation | en |
| dc.subject | photooxidation | en |
| dc.subject | protein microarray | en |
| dc.subject | 2-oxohistidine | en |
| dc.subject | kynurenine | en |
| dc.subject | reactive oxygen species | en |
| dc.subject | metal-catalyzed oxidation | en |
| dc.subject | photooxidation | en |
| dc.subject | protein microarray | en |
| dc.title | 合成含2-氧基組胺酸與犬尿胺酸之多肽並鑑定與其交互作用之蛋白質 | zh_TW |
| dc.title | Synthesis of 2-oxohistidine- and kynurenine-containing peptides and identification of their interacting proteins | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳健生,王宗興 | |
| dc.subject.keyword | 2-氧基組胺酸,犬尿胺酸,活性氧化物質,金屬催化氧化,光游離,蛋白質微陣列, | zh_TW |
| dc.subject.keyword | 2-oxohistidine,kynurenine,reactive oxygen species,metal-catalyzed oxidation,photooxidation,protein microarray, | en |
| dc.relation.page | 67 | |
| dc.identifier.doi | 10.6342/NTU201600417 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-07-21 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| Appears in Collections: | 化學系 | |
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| File | Size | Format | |
|---|---|---|---|
| ntu-104-1.pdf Restricted Access | 3.52 MB | Adobe PDF |
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