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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 王宗興 | zh_TW |
| dc.contributor.advisor | Tsung-Shing Wang | en |
| dc.contributor.author | 郭雨彤 | zh_TW |
| dc.contributor.author | Yu-Tong Kuo | en |
| dc.date.accessioned | 2025-08-20T16:28:30Z | - |
| dc.date.available | 2025-08-21 | - |
| dc.date.copyright | 2025-08-20 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-08-15 | - |
| dc.identifier.citation | (1) Schiff, P. B.; Fant, J.; Horwitz, S. B. Promotion of microtubule assembly in vitro by taxol. Nat. 1979, 277 (5698), 665-667.
(2) Hamel, E.; Del Campo, A.; Lowe, M.; Lin, C. Interactions of taxol, microtubule-associated proteins, and guanine nucleotides in tubulin polymerization. J. Biol. Chem. 1981, 256 (22), 11887-11894. (3) Wani, M. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J. Am. Chem. Soc. 1972, 19, 2325-2326. (4) Skwarczynski, M.; Noguchi, M.; Hirota, S.; Sohma, Y.; Kimura, T.; Hayashi, Y.; Kiso, Y. Development of first photoresponsive prodrug of paclitaxel. Bioorg. Med. Chem. Lett. 2006, 16 (17), 4492-4496. (5) Thapa, P.; Li, M.; Bio, M.; Rajaputra, P.; Nkepang, G.; Sun, Y.; Woo, S.; You, Y. Far-Red Light-Activatable Prodrug of Paclitaxel for the Combined Effects of Photodynamic Therapy and Site-Specific Paclitaxel Chemotherapy. J. Med. Chem. 2016, 59 (7), 3204-3214. (6) Gropeanu, R. A.; Baumann, H.; Ritz, S.; Mailänder, V.; Surrey, T.; Del Campo, A. Phototriggerable 2′, 7-caged paclitaxel. Plus One 2012, 7(9), 43657. (7) Goodson, H. V.; Jonasson, E. M. Microtubules and Microtubule-Associated Proteins. Cold Spring Harb. Perspect. Biol. 2018, 10 (6). (8) Schmitt, C.; Mauker, P.; Vepřek, N. A.; Gierse, C.; Meiring, J. C. M.; Kuch, J.; Akhmanova, A.; Dehmelt, L.; Thorn-Seshold, O. A Photocaged Microtubule-Stabilising Epothilone Allows Spatiotemporal Control of Cytoskeletal Dynamics. Angew. Chem. Int. Ed. 2024, 63 (43), e202410169. (9) Müller-Deku, A.; Meiring, J. C. M.; Loy, K.; Kraus, Y.; Heise, C.; Bingham, R.; Jansen, K. I.; Qu, X.; Bartolini, F.; Kapitein, L. C.; et al. Photoswitchable paclitaxel-based microtubule stabilisers allow optical control over the microtubule cytoskeleton. Nat. Commun. 2020, 11 (1), 4640. (10) Lee, M. M.; Gao, Z.; Peterson, B. R. Synthesis of a Fluorescent Analogue of Paclitaxel That Selectively Binds Microtubules and Sensitively Detects Efflux by P-Glycoprotein. Angew. Chem. Int. Ed. 2017, 56 (24), 6927-6931. (11) Jia, S.; Chang, C. J. A microtubule-localizing activity-based sensing fluorescent probe for imaging hydrogen peroxide in living cells. Bioorg. Med. Chem. Lett. 2021, 48, 128252. (12) Patchornik, A.; Amit, B.; Woodward, R. Photosensitive protecting groups. J. Am. Chem. Soc. 1970, 92 (21), 6333-6335. (13) O’Hagan, M. P.; Duan, Z.; Huang, F.; Laps, S.; Dong, J.; Xia, F.; Willner, I. Photocleavable Ortho-Nitrobenzyl-Protected DNA Architectures and Their Applications. Chem. Rev. 2023, 123 (10), 6839-6887. (14) Klán, P.; Šolomek, T.; Bochet, C. G.; Blanc, A.; Givens, R.; Rubina, M.; Popik, V.; Kostikov, A.; Wirz, J. Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy. Chem. Rev. 2013, 113 (1), 119-191. (15) Il'ichev, Y. V.; Schwörer, M. A.; Wirz, J. Photochemical reaction mechanisms of 2-nitrobenzyl compounds: methyl ethers and caged ATP. J. Am. Chem. Soc. 2004, 126 (14), 4581-4595. (16) Hung, H.-M.; Wang, T.-S. A. A Double Photocage Strategy to Construct Light-Controllable and Spatiotemporally Trackable Cathepsin B Activity-Based Probes. ACS Chem. Biol. 2021, 17 (1), 11-16. (17) de Silva, A. P.; Moody, T. S.; Wright, G. D. Fluorescent PET (Photoinduced Electron Transfer) sensors as potent analytical tools. Analyst 2009, 134 (12), 2385-2393. (18) Sun, W.; Li, M.; Fan, J.; Peng, X. Activity-Based Sensing and Theranostic Probes Based on Photoinduced Electron Transfer. Acc Chem Res. 2019, 52 (10), 2818-2831. (19) Shi, R.; Huang, L.; Duan, X.; Sun, G.; Yin, G.; Wang, R.; Zhu, J.-j. Selective imaging of cancer cells with a pH-activatable lysosome-targeting fluorescent probe. Anal. Chim. Acta 2017, 988, 66-73. (20) Wu, Y.; Peng, X.; Guo, B.; Fan, J.; Zhang, Z.; Wang, J.; Cui, A.; Gao, Y. Boron dipyrromethene fluorophore based fluorescence sensor for the selective imaging of Zn(ii) in living cells. Org. Biomol. Chem. 2005, 3 (8), 1387-1392. (21) Lin, Q.; Bao, C.; Yang, Y.; Liang, Q.; Zhang, D.; Cheng, S.; Zhu, L. Highly discriminating photorelease of anticancer drugs based on hypoxia activatable phototrigger conjugated chitosan nanoparticles. Adv Mater. 2013, 25 (14), 1981-1986. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/98968 | - |
| dc.description.abstract | 我們開發了一種具備雙重功能、可透過光啟動的微管探針，其設計基於已知具有穩定微管作用的藥物 paclitaxel (PTX)。此探針結合了兩種光保護基（photocage）：DEACM 與一系列 o-nitrobenzyl（oNB）衍生物，能同時光控其生物活性與螢光訊號。
我們合成並系統性評估了六種 oNB 衍生 quencher 的光物理與光化學特性。實驗結果顯示，2,4-dinitrobenzyl (2,4-DNB) 具有最強的螢光抑制能力，而 2,6-dinitrobenzyl (2,6-DNB) 則展現最快的光解速率。 生物實驗證實，double-caged PTX 探針在照光前毒性明顯降低，照光後則可回復其對微管的作用力。雖然在螢光顯微鏡下觀察仍受限於光漂白與訊號微弱的問題，預期未來透過導入如 AzCM 等更穩定的螢光分子，能有效提升探針表現。 本研究提出一項可光控的雙重保護基策略，成功應用於微管探針的建構上，為細胞內微管相關機制的研究提供了有力的化學生物學工具。 | zh_TW |
| dc.description.abstract | We have developed a dual-functional, light-activated microtubule probe based on paclitaxel (PTX), a well-characterized microtubule-stabilizing agent. Our probe integrates two photocages—DEACM and a series of o-nitrobenzyl (oNB) derivatives—allowing simultaneous optical control over both biological activity and fluorescence signal.
A library of six oNB-derived quenchers was synthesized and evaluated for their photophysical and photochemical performance. Among them, 2,4-dinitrobenzyl (2,4-DNB) demonstrated the most efficient fluorescence quenching, while 2,6-dinitrobenzyl (2,6-DNB) exhibited the fastest photolysis rate. Biological assays confirmed that the double-caged PTX probes displayed reduced cytotoxicity prior to light activation and restored microtubule activity post-irradiation. Although fluorescence imaging using microscopy encountered issues such as photobleaching and limited signal, future optimization—including the use of more photostable fluorophores like AzCM—is anticipated to enhance performance. In summary, we present a dual-caging strategy for constructing light-controllable microtubule probes. This platform provides a valuable chemical biology tool for dissecting microtubule-mediated processes in live cells. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-08-20T16:28:30Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-08-20T16:28:30Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 摘要 I
Abstract II Contents IV List of Figures VI Abbreviations VIII Chapter 1 Introduction 1 Paclitaxel 1 Microtubule 2 Photocage 3 Dual-caging strategy 3 Photo-induced electron transfer (PET) 5 Chapter 2 Results and discussions 9 2.1 Molecular design 9 2.2 Synthesis 15 2.3 Photophysical properties 16 2.4 Biological Validation 27 Chapter 3 Conclusion and Perspectives 31 Chapter 4 Materials and Methods 33 4.1 General Methods and Instrumentations 33 4.2 In vitro experiments 34 4.3 In vivo experiments 37 4.4 Synthesis and characterizations of compounds 39 Appendix 66 Flow cytometry 66 HPLC chromatograph 70 NMR spectra 74 Reference 102 | - |
| dc.language.iso | en | - |
| dc.subject | 光保護基團 | zh_TW |
| dc.subject | 紫杉醇 | zh_TW |
| dc.subject | 螢光 | zh_TW |
| dc.subject | 微管 | zh_TW |
| dc.subject | 光誘導電子轉移 | zh_TW |
| dc.subject | tubulin | en |
| dc.subject | photo-induced electron transfer | en |
| dc.subject | o-nitrobenzyl | en |
| dc.subject | fluorescence | en |
| dc.subject | photocage | en |
| dc.subject | paclitaxel | en |
| dc.subject | microtubule | en |
| dc.title | 藉由光保護基調變優化具光可控性的紫杉醇螢光探針 | zh_TW |
| dc.title | Optimize Light-Controlled Restore of Paclitaxel Activity and Fluorescence through Dual-Photocage Tuning | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 謝俊結;魏妊亘 | zh_TW |
| dc.contributor.oralexamcommittee | Jiun-Jie Shie;Jen-Hsuan Wei | en |
| dc.subject.keyword | 光保護基團,紫杉醇,螢光,微管,光誘導電子轉移, | zh_TW |
| dc.subject.keyword | photocage,paclitaxel,fluorescence,microtubule,tubulin,o-nitrobenzyl,photo-induced electron transfer, | en |
| dc.relation.page | 103 | - |
| dc.identifier.doi | 10.6342/NTU202504300 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-08-15 | - |
| dc.contributor.author-college | 理學院 | - |
| dc.contributor.author-dept | 化學系 | - |
| dc.date.embargo-lift | N/A | - |
| Appears in Collections: | 化學系 | |
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| File | Size | Format | |
|---|---|---|---|
| ntu-113-2.pdf Restricted Access | 8.2 MB | Adobe PDF |
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