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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77200完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳平 | zh_TW |
| dc.contributor.advisor | Richard Ping Cheng | en |
| dc.contributor.author | 陳庭萱 | zh_TW |
| dc.contributor.author | Ting-Hsuan Chen | en |
| dc.date.accessioned | 2021-07-10T21:50:34Z | - |
| dc.date.available | 2024-08-19 | - |
| dc.date.copyright | 2019-08-26 | - |
| dc.date.issued | 2019 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | Chapter 1
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Effect of citrulline side chain length on β-hairpin stability, and towards targeting HIV-related RNA motifs. M.S. Thesis, National Taiwan University, 2015. 16. Cheng, R. P.; Weng, Y.-J.; Wang, W.-R.; Koyack, M. J.; Suzuki, Y.; Wu, C.-H.; Yang, P.-A.; Hsu, H.-C.; Kuo, H.-T.; Girinath, P.; Fang, C.-J. Helix formation and capping energetics of arginine analogs with varying side chain length. Amino Acids 2012, 43, 195-206. 17. Edelhoch, H. Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry 1967, 6, 1948-1954. 18. Pace, C. N.; Vajdos, F.; Fee, L.; Grimsley, G.; Gray, T. How to measure and predict the molar absorption-coefficient of a protein. Protein Sci. 1995, 4, 2411-2423. Chapter 3 1. Gupta, B.; Levchenko, T. S.; Torchilin, V. P. Intracellular delivery of large molecules and small particles by cell-penetrating proteins and peptides. Adv. Drug Deliv. Rev. 2005, 57, 637-651. 2. Schwarze, S. R.; Ho, A.; Vocero-Akbani, A.; Dowdy, S. F. 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Acta, Pt. A: Mol. Spectrosc. 1995, 51, L7-L21. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77200 | - |
| dc.description.abstract | 愛滋病是由人類免疫缺乏病毒（HIV）所導致，而關於病毒以及治療方式的研究也在近幾十年來不斷有新結果。其中一種可能的治療方式是以干擾Tat蛋白與TAR RNA之間的交互作用力，進而影響病毒的繁衍；這樣的構思已應用在先前的研究中並設計出一種以Tat蛋白為模版的胜肽—TatC4。TatC4具有和TAR RNA的高度結合力，但其專一性不足，造成TatC4抑制Tat-TAR交互作用的能力不如預期。所以本次研究是希望透過更改胺基酸側鏈的長度與電荷，可以增進Tat衍生胜肽對TAR RNA的專一性。
實驗方式是以凝膠電泳（Electrophoretic mobility shift assay）來代表胜肽與TAR RNA的結合度；根據Tat衍生胜肽與對照組的比較，新設計出來的胜肽中有部分衍生胜肽對TAR RNA具有比較高的專一性。同時也使用流式細胞儀，針對與TAR RNA有較高親和性與專一性的Tat衍生胜肽進行細胞穿膜實驗，結果顯示Tat衍生胜肽皆具有較高的穿膜能力。由此可知，側鏈長度與電荷的更動不只影響胜肽與TAR RNA的結合度，也同時影響胜肽的細胞穿膜能力。 | zh_TW |
| dc.description.abstract | HIV (Human Immunodeficiency virus) has been studied for decades, and research on developing drugs for treating HIV infection has been ongoing. Interfering with the interaction between TAR RNA and Tat-protein might be a therapeutically viable strategy, which gave rise to the development of peptide TatC4 to bind TAR RNA in the Cheng lab (Org. Biomol. Chem. 2015, 13, 11096). Unfortunately, the ability of TatC4 to inhibit Tat-TAR mediated protein production didn’t meet our expectations. The results suggested that the specificity for binding TAR remained to be improved. This lack of specificity could perhaps be remediated by simultaneously changing the side chain length and charge of the Arg residues in the Tat-derived peptide. Accordingly, a series of Tat-derived peptides with Arg side chain modifications have been synthesized by solid phase methods and purified. The binding of the peptides to TAR RNA was investigated by EMSA (electrophoretic mobility shift assay). Some of the Tat-derived peptides showed enhanced TAR RNA binding affinity and specificity. Four peptides with higher binding specificity or affinity were chosen for cellular uptake studies, which all showed higher cellular uptake compared to the native peptide. Overall, the research should contribute to developing molecules to treat HIV infections. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-10T21:50:34Z (GMT). No. of bitstreams: 1 ntu-108-R06223133-1.pdf: 5645923 bytes, checksum: 9f923c0ecd70d9073d1fc3af669dcec8 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 謝誌 i
中文摘要 ii Abstract iii Table of Contents v List of Figures vii List of Schemes ix List of Tables x Abbreviation i Chapter 1 1 1-1. Central Dogma of Molecular Biology 2 1-2. Proteins 2 1-3. Post-Translational Modification 3 1-4. RNA Recognition 4 1-5. Cell Penetration 6 1-6. Thesis Overview 7 1-7. Reference 9 Chapter 2 13 2-1. Introduction 14 HIV TAR RNA and Tat Protein 14 Side Chain Effects on TAR RNA Binding of Tat-Derived Peptides 15 Design and Development of TatC4 17 2-2. Results and Discussion 18 Peptide Design 18 Peptide Synthesis 23 Electrophoretic Mobility Shift Assays 34 2-3. Conclusion 48 2-4. Future Aspects 48 2-5. Acknowledgements 49 2-6. Experimental Section 49 2-7. Reference 86 Chapter 3 89 3-1. Introduction 90 Cell Penetrating Peptides 90 Cellular Uptake of Tat Peptide 91 3-2. Results and Discussion 92 Peptide Design 92 Peptide Synthesis 93 Cellular Uptake Assays 98 Cytotoxicity 107 3-3. Conclusion 108 3-4. Acknowledgements 109 3-5. Experimental Section 109 3-6. Reference 127 | - |
| dc.language.iso | en | - |
| dc.subject | TAR核糖核酸 | zh_TW |
| dc.subject | 人類免疫缺乏病毒 | zh_TW |
| dc.subject | Tat蛋白 | zh_TW |
| dc.subject | 專一性 | zh_TW |
| dc.subject | 側鏈 | zh_TW |
| dc.subject | Tat protein | en |
| dc.subject | HIV | en |
| dc.subject | TAR RNA | en |
| dc.subject | Side chain | en |
| dc.subject | Specificity | en |
| dc.subject | Cellular uptake | en |
| dc.title | 側鏈修飾對Tat衍生胜辨認核糖核酸與細胞穿透之影響 | zh_TW |
| dc.title | Effect of Side Chain Modifications of Tat-derived Peptides on RNA Recognition and Cellular Uptake | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 107-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 洪嘉呈;黃人則;陳佩燁 | zh_TW |
| dc.contributor.oralexamcommittee | ;; | en |
| dc.subject.keyword | 人類免疫缺乏病毒,Tat蛋白,TAR核糖核酸,側鏈,專一性, | zh_TW |
| dc.subject.keyword | HIV,Tat protein,TAR RNA,Side chain,Specificity,Cellular uptake, | en |
| dc.relation.page | 128 | - |
| dc.identifier.doi | 10.6342/NTU201903850 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2019-08-16 | - |
| dc.contributor.author-college | 理學院 | - |
| dc.contributor.author-dept | 化學系 | - |
| 顯示於系所單位： | 化學系 | |
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