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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 羅禮強(Lee-Chiang Lo) | |
| dc.contributor.author | Han-Yu Chen | en |
| dc.contributor.author | 陳函郁 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:46:35Z | - |
| dc.date.available | 2021-08-06 | |
| dc.date.available | 2022-11-24T03:46:35Z | - |
| dc.date.copyright | 2021-08-06 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2021-07-23 | |
| dc.identifier.citation | Jeffery, D. A.; Bogyo, M. Chemical Proteomics and Its Application to Drug Discovery. Curr. Opin. Biotechnol. 2003, 14, 87-95. Patterson, S. D.; Aebersold, R. H. Proteomics: The First Decade and Beyond. Nat. Genet. 2003, 33, 311-323. O’Farrel, P. H. High Resolution Two-Dimensional Electrophoresis of Proteins. J. Biol. Chem. 1975, 250, 4007-4021. Klose, J. Protein Mapping by Combined Isoelectric Focusing and Electrophoresis of Mouse Tissues. Humangenetik 1975, 26, 231-243. Cravatt, B. F.; Wright, A. T.; Kozarich, J. W. Activity-Based Protein Profiling: From Enzyme Chemistry to Proteomic Chemistry. Annu. Rev. Biochem. 2008, 77, 383-414. Speers, A. E.; Cravatt, B. F. Chemical Strategies for Activity-Based Proteomics. ChemBioChem 2004, 5, 41-47. Jessani, N.; Cravatt, B. F. The Development and Application of Methods for Activity-Based Protein Profiling. Curr. Opin. Biol. 2004, 8, 54-59. Heal, W. P.; Tam Dang, T. H.; Tate, E. W. Activity-Based Probes: Discovering New Biology and New Drug Targets. Chem. Soc. Rev. 2011, 40, 246-257. Codelli, J. A.; Baskin, J. M.; Agard, N. J.; Bertozzi, C. R. Second-Generation Difluorinated Cyclooctynes for Copper-Free Bodipy Chemistry. J. Am. Chem. Soc. 2008, 130, 11486-11493. Salisbury, C. M.; Cravatt, B. F. Click Chemistry-Led Advances in High Content Functional Proteomics. QSAR Comb. Sci. 2007, 26, 1229-1238. Chalker, J. M.; Wood, C. S. C.; Davis, B. G. A Convenient Catalyst for Aqueous and Protein Suzuki-Miyaura Cross-Coupling. J. Am. Chem. Soc. 2009, 131, 16346-16347. Lee, B. Y.; Park, S. R.; Jeon, H. B.; Kim, K. S. A New Solvent System for Efficient Synthesis of 1,2,3-Triazoles. Tetrahedron Lett. 2006, 47, 5105-5109.Khiar-Fernández, N.; Macicior, J.; Marcos-Ramiro, B.; Ortega-Gutiérrez, S. Chemistry for the Identification of Therapeutic Targets: Recent Advances and Future Directions. Eur. J. Org. Chem. 2021, 9, 1307-1320. Mason, R. W.; Wilcox, D.; Wikstorm, P.; Shaw, E. N. The Identification of Active Forms of Cysteine Proteinases in Kirsten-Virus-Transformed Mouse Fibroblasts by Use of a Specific Radiolabelled Inhibitor. Biochem. J. 1989, 257, 125-129. Liu, Y.; Patricelli, M. P.; Cravatt, B. F. Activity-Based Protein Profiling: The Serine Hydrolases. Proc. Natl. Acad. Sci. 1999, 96, 14694-14699. Obiamaka, O.; Causey, C. P.; Jones, J. E.; Thompson, P. R. Activity-Based Protein Profiling of Protein Arginine Methyltransferase. ACS Chem. Biol. 2011, 6, 1127-1135. Mulder, M. P.; Witting, K.; Berlin, I.; Pruneda, J. N.; Wu, K. P.; Chang, J. G.; Merkx, R.; Bialas, J.; Groettrup, M.; Vertegaal, A. C.; Schulman, B. A.; Komander, D.; Neefjes, J.; Oualid, F.; Ovaa, H. A Cascading Activity-Based Probe Sequentially Targets E1–E2–E3 Ubiquitin Enzymes. Nat. Chem. Biol. 2016, 12, 523-530. Patricelli, M. P.; Katrin Szardenings, A.; Liyanage, M.; Nomanbhoy, T. K.; Wu, M.; Weissig, H.; Aban, A.; Chun, D.; Tanner, S.; Kozarich, J. W. Functional Interrogation of the Kinome Using Nucleotide Acyl Phosphates. Biochemistry 2007, 46, 350-358. Lo, L. C.; Pang, T. L.; Kuo, C. H.; Chiang, Y. L.; Wang, H. Y.; Lin, J. J. Design and Synthesis of Class-Selective Activity Probes for Protein Tyrosine Phosphatases. J. Proteome Res. 2002, 1, 35-40. Bogyo, M.; Mcmaster, J. C.; Gaczynska, M.; Tortorella, D.; Goldberg, A. L.; Ploega, H. Covalent Modification of the Active Site Threonine of Proteasomal B Subunits and the Escherichia Coli Homolog HslV by A New Class of Inhibitors. Proc. Natl. Acad. Sci. 1997, 94, 6629-6634. Keresztessy, Z.; Kiss, L.; Hughes, M. H. Co-purification from Escherichia Coli of A Plant β-Glucuronidase-Glutathione S-Transferase Fusion Protein and the Bacterial Chaperonin GroEL. Arch. Biochem. Biophys. 1994, 315, 323-330. Vocadlo, D. J.; Bertozzi, C. R. A Strategy for Functional Proteomic Analysis of Glycosidase Activity from Cell Lysates. Angew. Chem. Int. Ed. 2004, 43, 5338-5342. Dempsey, L. A.; Brunn, G. J.; Platt, J. L. Heparanase, Potential Regulator of Cell-matrix Interactions. Trends Biol. Sci. 2000, 25, 349-351. Kwan, D. H.; Chen, H. M.; Ratananikom, K.; Hancock, S. M.; Watanabe, Y.; Kongsaeree, P. T.; Samuels, A. L.; Withers, S. G. Self-Immobilizing Fluorogenic Imaging Agents of Enzyme Activity. Angew. Chem. Int. Ed. 2011, 50, 300-303. Raben, N.; Plotz, P.; Byrne, B. J. Acid Alpha-Glucosidase Deficiency. Curr. Mol. Med. 2002, 2, 145-166. Humphries, M. J.; Matsumoto, K.; White, S. L.; Olden, K. Inhibition of Experimental Metastasis by Castanospermine in Mice. Cancer Res. 1986, 46, 5215-5222. Karpas, A.; Fleet, G.; Dwek, R. A.; Petursson, S.; Namgoong, S. K.; Ramsden, N. G.; Jacob, G. S.; Rademacher, T. W. Aminosugar Derivatives as Potential Anti-Human Immunodeficiency Virus Agents. Proc. Natl. Acad. Sci. 1988, 85, 9229-9233. Malm, D.; Nilssen, O. Alpha-mannosidosis. Orphanet J. Rare Dis. 2008, 3, 21-30. Barton, N. W.; Furbish, F. S.; Murray, G. J.; Garfield, M.; Brady, R. O. Therapeutic Response to Intravenous Infusions of Glucocerebrosidase in A Patient with Gaucher Disease. Proc. Natl. Acad. Sci. 1990, 87, 1913-1916. Merino-Trigo, A.; Rodriguez-Berrocal, F. J.; Miguel, E. Activity and Properties of Alpha-L-Fucosidase are Dependent on the State of Enterocytic Differentiation of HT-29 Colon Cancer Cells. Int. J. Biochem. Cell Biol. 2002, 34, 1291-1303. Giardina, M. G.; Matarazzo, M.; Varriale, A.; Morante, R.; Napoli, A.; Martino, R. Serum Alpha-L-Fucosidase. A Useful Marker in the Diagnosis of Hepatocellular Carcinoma. Cancer 1992, 70, 1044-1048. Reichert, C. M. Synthesis of p-Nitrophenyl 2-O-α-D-Mannopyranosyl-α-D-Mannopyranoside. Carbohydr. Res. 1979, 77, 141-147. Kolter, T.; Sears, P.; Wong, C. H. Enzyme Action in Glycoprotein Synthesis. Cell. Mol. Life Sci. 1998, 54, 223-252. Cheng, T. C.; Roffler, S. R.; Tzou, S. C.; Chuang, K. H.; Su, Y. C.; Chuang, C. H.; Kao, C. H.; Chen, C. S.; Harn, I. H.; Liu, K. Y.; Cheng, T. L.; Leu, Y. L. An Activity-Based Near-Infrared Glucuronide Trapping Probe for Imaging β-Glucuronidase Expression in Deep Tissues. J. Am. Chem. Soc. 2012, 134, 3103-3110. Zlokarnik, G.; Negulescu, P. A.; Knapp, T. E.; Mere, K. L.; Burres, N.; Feng, L.; Whitney, M.; Roemer, K.; Tsien, R. Y. Quantitation of Transcription and Clonal Selection of Single Living Cells with β-Lactamase as Reporter. Science 1998, 279, 84-88. Shi, Z. D.; Motabar, O.; Goldin, E.; Liu, K.; Southall, N.; Sidransky, E.; Austin, C. P.; Griffiths, G. L.; Zheng, W. Synthesis and Characterization of a New Fluorogenic Substrate for Alpha-Galactosidase. Anal. Bioanal. Chem. 2009, 394, 1903-1909. Kalesh, K. A.; Tan, L. P.; Lu, K.; Gao, L. Q.; Wang, J. G.; Yao, S. Q. Peptide-Based Activity-Based Probes for Target-Specific Profiling of Protein Tyrosine Phosphatases. Chem. Commun. 2010, 46, 589-591. Chang, T.; Cheng, C. M.; Su, Y. Z.; Lee, W. T.; Hsu, J. S.; Liu, G. C.; Cheng, T. L.; Wang, Y. M. Synthesis and Characterization of A New Bioactivated Paramagnetic Gadolinium(III) Complex [Gd(DOTA-FPG)(H2O)] for Tracing Gene Expression. Bioconjugate Chem. 2007, 18, 1716-1727. Garland, M.; Yim, J. J.; Bogyo, M. A Bright Future for Precision Medicine: Advances in Fluorescent Chemical Probe Design and Their Clinical Application. Cell Chem. Biol. 2016, 23, 122-136. Polaske, N. W.; Kelly, B. D.; Ashworth-Sharpe, J.; Bieniarz, C. Quinone Methide Signal Amplification: Covalent Reporter Labeling of Cancer Epitopes Using Alkaline Phosphatase Substrates. Bioconjugate Chem. 2016, 27, 660-666. Janda, K. D.; Lo, L. C.; Lo, C. H. L.; Sim, M. M.; Wang, R.; Wong, C. H.; Lerner, R. A. Chemical Selection for Catalysis in Combinatorial Antibody Libraries. Science 1997, 275, 945-948. Tsai, C. H.; Li, Y. K.; Lo, L. C. Design and Synthesis of Activity Probes for Glycosidases. Org. Lett. 2002, 4, 3607-3610. Hsu, Y. L.; Nandakumar, M.; Lai, H. Y.; Chou, T. C.; Chu, C. Y.; Lin, C. H.; Lo, L. C. Development of Activity-Based Probes for Imaging Human α-L-Fucosidases in Cells. J. Org. Chem. 2015, 80, 8458-8463. Kai, H.; Hinou, H.; Nishimura, S. I. A Highly Potent, Selective, Long-Lasting and Orally Activedipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes. Bioorg. Med. Chem. 2012, 20, 2739-2746. Didenko, V. V. DNA Probes Using Fluorescence Resonance Energy Transfer (FRET): Designs and Applications. BioTechniques 2001, 31, 1106-1121. Ueda, Y.; Kwok, S.; Hayashi, Y. Application of FRET Probes in the Analysis of Neuronal Plasticity. Front. Neural Circuits 2013, 7, 1-19. Yuan, L.; Lin, W. Y.; Zheng, K. B.; Zhu, S. S. FRET-Based Small-Molecule Fluorescent Probes: Rational Design and Bioimaging Applications. Acc. Chem. Res. 2013, 46, 1462-1473. Lee, A.; Chin, J.; Park, O. K.; Chung, H.; Kim, J. W.; Yoona, S. Y.; Park, K. A Novel Near-Infrared Fluorescence Chemosensor for Copper Ion Detection using Click Ligation and Energy Transfer. Chem. Commun. 2013, 49, 5969-5971. Nagano, T.; Komatsu, T.; Kikuchi, K.; Takakusa, H.; Hanaoka, K.; Ueno, T.; Kamiya, M.; Urano, Y. Design and Synthesis of an Enzyme Activity-Based Labeling Molecule with Fluorescence Spectral Change. J. Am. Chem. Soc. 2006, 128, 15946-15947. Redy, O.; Kisin-Finfer, E.; Sella, E.; Shabat, D. A Simple FRET-Based Modular Design for Diagnostic Probes. Org. Biomol. Chem. 2012, 10, 710-715. Kalidasan, K.; Su, Y.; Wu, X.; Yao, S. Q.; Uttamchandani, M. Fluorescence-Activated Cell Sorting and Directed Evolution of α-N-Acetylgalactosainidases Using a Quenched Activity-Based Probe. Chem. Commun. 2013, 49, 7237-7239.Itahana, K.; Itahana, Y.; Dimri, G. P. Colorimetric Detection of Senescence-Associated β-Galactosidase. Methods Mol. Biol. 2013, 965, 143-156. Gu, K.; Xu, Y.; Li, H.; Guo, Z.; Zhu, S.; Shi, P.; James, T. D.; Tian, H.; Zhu, W. H. Real-Time Tracking and In Vivo Visualization of β-Galactosidase Activity in Colorectal Tumor with a Ratiometric Near-Infrared Fluorescent Probe. J. Am. Chem. Soc. 2016, 138, 5334-5340. Zhu, R.; Wang, S.; Xue, Z.; Han, J.; Han, S. Senescence-Associated Sialidase Revealed by an Activatable Fluorescence-On Labeling Probe. Chem. Commun. 2018, 54, 11566-11569. Lo, L. C.; Lo, C. H. L.; Janda, K. D.; Kassel, D. B.; Raushel, F. M. A Versatile Mechanism Based Reaction Probe for the Direct Selection of Biocatalystss. Bioorg. Med. Chem. Lett. 1996, 6, 2117-2120. Hsu, Y. L.; Nandakumar, M.; Lai, H. Y.; Chou, T. C.; Chu, C. Y.; Lin, C. H.; Lo, L. C. Development of Activity-Based Probes for Imaging Human α-L-Fucosidases in Cells. J. Org. Chem. 2015, 80, 8458-8463. Forster, T. Transfer Mechanisms of Electronic Excitation Energy. Radiat. Res. Suppl. 1960, 2, 326-339. Wu, P.; Brand, L. Resonance Energy Transfer: Methods and Applications. Anal. Biochem. 1994, 218, 1-13. Marras, S. A. E. Interactive Fluorophore and Quencher Pairs for Labeling Fluorescent Nucleic Acid Hybridization Probes. Mol. Biotechnol. 2008, 38, 247-255. Marras, S. A. E.; Kramer, F. R.; Tyagi, S. Chemical Incorporation of 1-Methyladenosine into Oligonucleotides. Nucleic Acids Res. 2002, 30, 122-129. Huisgen, R. 1,3-Dipolar Cycloadditions. Angew. Chem. Int. Ed. 1963, 2, 565-598. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes. Angew. Chem. Int. Ed. 2002, 41, 2596-2599. Tornoe, C. W.; Christensen, C.; Meldal, M. Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides. J. Org. Chem. 2002, 67, 3057-3064. Shaffer, S. A.; Baker-Lee, C.; Kennedy, J.; Lai, M. S.; de Vries, P.; Buhler, K.; Singer, J. W. In Vitro and In Vivo Metabolism of Paclitaxel Poliglumex: Identification of Metabolites and Active Proteases. Cancer Chemother. Pharmacol. 2007, 59, 537-548. Hein, C. D.; Liu, X. M.; Wang, D. Click Chemistry, A Powerful Tool for Pharmaceutical Sciences. Pharm. Res. 2008, 25, 2216-2230. Jewett, J. C.; Bertozzi, C. R. Cu-Free Click Cycloaddition Reactions in Chemical Biology. Chem. Soc. Rev. 2010, 39, 1272-1279. Schieber, C.; Bestetti, A.; Lim, J. P.; Ryan, A. D.; Nguyen, T. L.; Eldridge, R.; White, A. R.; Gleeson, P. A.; Donnelly, P. S.; Williams, S. J.; Mulvaney, P. Conjugation of Transferrin to Azide-Modified CdSe/ZnS Core-Shell Quantum Dots using Cyclooctyne Click Chemistry. Angew. Chem. Int. Ed. 2012, 51, 10523-10527. O’Brien, J. G. K.; Chintala, S. R.; Fox, J. M. Stereoselective Synthesis of Bicyclo[6.1.0]nonene Precursors of the Bioorthogonal Reagents s-TCO and BCN. J. Org. Chem. 2018, 83, 7500-7503. Gential, G. P. P.; Ho, N. I.; Chiodo, F.; Meeuwenoord, N.; Ossendorp, F.; Overkleeft, H. S.; van der Marel, G. A.; Filippov, D. V. Synthesis and Evaluation of Fluorescent Pam3Cys Peptide Conjugates. Bioorg. Med. Chem. Lett. 2016, 26, 3641-3645. Jia, X.; Chen, Q.; Yang, Y. F.; Tang, Y.; Wang, R.; Xu, Y. F.; Zhu, W.; Qian, X. FRET-Based Mito-Specific Fluorescent Probe for Ratiometric Detection and Imaging of Endogenous Peroxynitrite: Dyad of Cy3 and Cy5. J. Am. Chem. Soc. 2016, 138, 10778-10781. Sampedro, A.; Ramos-Torres, A.; Schwoppe, C.; Miick, L.; Helmers, I.; Bort, A.; Diaz Laviada, I.; Fernandez, G. Hierarchical Self-Assembly of BODIPY Dyes as a Tool to Improve the Antitumor Activity of Capsaicin in Prostate Cancer. Angew. Chem. Int. Ed. 2018, 57, 17235-17239. Gaykema, W. P. J.; Hol, W. G. J.; Vereijken, J. M.; Soeter, N. M.; Bak, H. J.; Beintema, J. J. A Structure of the Copper-containing, Oxygen-carrying Protein Panulirus Interruptus Haemocyanin. Nature 1984, 309, 23-29. Kempe, K.; Krieg, A.; Becer, C. R.; Schubert, U. S. “Clicking” on/with Polymers: A Rapidly Expanding Field for the Straightforward Preparation of Novel Macromolecular Architectures. Chem. Soc. Rev. 2012, 41, 176-191. Hua, Y.; Flood, A. H. Click Chemistry Generates Privileged CH Hydrogen-Bonding Triazoles: The Latest Addition to Anion Supramolecular Chemistry. Chem. Soc. Rev. 2010, 39, 1262-1271. Pedersen, D. S.; Abell, A. E. 1,2,3-Triazoles in Peptidomimetic Chemistry. J. Org. Chem. 2011, 13, 2399-2411. Egami, H.; Kamisuki, S.; Dodo, K.; Asanuma, M.; Hamashimab, Y.; Sodeoka, M. Catch and Release of Alkyne-tagged Molecules in Water by a Polymer-Supported Cobalt Complex. Org. Biomol. Chem. 2011, 9, 7667-7670. Nakatani, K.; Kobori, A.; Kumasawaa, H.; Saito, I. Highly Sensitive Detection of GG Mismatched DNA by Surfaces Immobilized Naphthyridine Dimer through Poly(ethylene oxide) Linkers. Bioorg. Med. Chem. Lett. 2004, 14, 1105-1108. Chevalier, A.; Renard, P. Y.; Romieu, A. Straightforward Synthesis of Bioconjugatable Azo Dyes. Tetrahedron Lett. 2014, 55, 6764-6768. Kuo, S. Y.; Liu, C. Y.; Balamurugan, R.; Zhang, Y. S.; Fitriyani, S.; Liu, J. H. Dual-responsive ALS-type Organogelators Based on Azobenzene-Cholesteryl Conjugates and Their Self-Assemblies. New J. Chem. 2017, 41, 15555-15563. Winchester, B. G. Lysosomal Metabolism of Glycoconjugates. Subcell. Biochem. 1996, 27, 191-238. Wang, K.; Guo, W.; Li, N.; Shi, J.; Zhang, C.; Lau, W. Y.; Wu, M.; Cheng, S. Alpha- L-Fucosidase as a Prognostic Indicator for Hepatocellular Carcinoma Following Hepatectomy. Br. J. Cancer 2014, 110, 1811-1819. Abdel-Aleem, H.; Ahmed, A.; Sabra, A. M.; Zakhari, M.; Soliman, M.; Hamed, H. Serum Alpha-L-Fucosidase Enzyme Activity in Ovarian and Other Female Genital Tract Tumors. Int. J. Gynecol. Obstet. 1996, 55, 273-279. Bukofzer, S.; Stass, P. M.; Kew, M. C.; de Beer, M.; Groeneveld, H. T. Alpha-L-Fucosidase As A Serum Marker of Hepatocellular Carcinoma in Southern African Blacks. Br. J. Cancer 1989, 59, 417-420. Liu, T. W.; Ho, C. W.; Huang, H. H.; Chang, S. M.; Popat, S. D.; Wang, Y. T.; Wu, M. S.; Chen, Y. J.; Lin, C. H. Role for α-L-fucosidase in the Control of Helicobacter pylori-Infected Gastric Cancer Cells. Proc. Natl. Acad. Sci. 2009, 106, 14581-14586. Hou, X.; Peng, J.; Zeng, F.; Yu, C.; Wu, S. An Anthracenecarboximide Fluorescent Probe for In Vitro and In Vivo Ratiometric Imaging of Endogenous Alpha-L-Fucosidase for Hepatocellular Carcinoma Diagnosis. Mater. Chem. Front. 2017, 1, 660-667. Jewett, J. C.; Bertozzi, C. R. Synthesis of a Fluorogenic Cyclooctyne Activated by Cu-Free Click Chemistry. Org. Lett. 2011, 13, 5937-5939. Sawa, M.; Hsu, T. L.; Itoh, T.; Sugiyama, M.; Hanson, S. R.; Vogt, P. K.; Wong, C. H. Glycoproteomic Probes for Fluorescent Imaging of Fucosylated Glycans In Vivo. Proc. Natl. Acad. Sci. 2006, 103, 12371-12376. Benjamin, J. L.; Jr Sumpter, R.; Levine, B.; Hooper, L. V. Intestinal Epithelial Autophagy is Essential for Host Defense Against Invasive Bacteria. Cell Host Microbe 2013, 13, 723-734. Nandakumar, M.; Hsu, Y. L.; Lin, C. Y.; Lo, C.; Lo, L. C.; Lin, C. H. Detection of Human α-L-Fucosidases by a Quinone Methide-Generating Probe: Enhanced Activities in Response to Helicobacter pylori Infection. ChemBioChem 2015, 16, 1555-1559. Drake, C. R.; Miller, D. C.; Jones, E. F. Activatable Optical Probes for the Detection of Enzymes. Curr. Org. Synth. 2011, 8, 498-520. You, Y.; Tataurov, A. V.; Owczarzy, R. Measuring Thermodynamic Details of DNA Hybridization Using Fluorescence. Biopolymers 2011, 7, 472-486. Rushworth, J. L.; Montgomery, K. S.; Cao, B.; Brown, R.; Dibb, N. J.; Nilsson, S. K.; Chiefari, J.; Fuchte, M. J. Glycosylated Nanoparticles Derived from RAFT Polymerization for Effective Drug Delivery to Macrophages. ACS Appl. Bio Mater. 2020, 3, 5775-5786. Vudhgiri, S.; Prasad, R. B. N.; Poornachandra, Y.; Kumar, C. G.; Anjaneyulu, E.; Sirisha, K.; Reddy Jala, R. C. The Impact of Sugar and Fatty Acid on the Bioactivity of N-Fatty Acyl-L-Tyrosine Aglycone. J. Chem. Sci. 2017, 129, 663-677. Zhao, G.; Yao, W.; Mauro, J. N.; Ngai, M. Y. Excited-State Palladium-Catalyzed 1,2-Spin-Center Shift Enables Selective C-2 Reduction, Deuteration, and Iodination of Carbohydrates. J. Am. Chem. Soc. 2021, 143, 1728-1734. Morelli, L.; Bernardi, A.; Sattin, S. Synthesis of Potential Allosteric Modulators of Hsp90 by Chemical Glycosylation of Eupomatenoid-6. Carbohydr. Res. 2014, 390, 33-41. Schieber, C.; Bestetti, A.; Lim, J. P.; Ryan, A. D.; Nguyen, T. L.; Eldridge, R.; White, A. R.; Gleeson, P. A.; Donnelly, P. S.; Williams, S. J.; Mulvaney, P. Conjugation of Transferrin to Azide-Modified CdSe/ZnS Core-Shell Quantum Dots using Cyclooctyne Click Chemistry. Angew. Chem. Int. Ed. 2012, 51, 10523-10527. O’Brien, J. G. K.; Chintala, S. R.; Fox, J. M. Stereoselective Synthesis of Bicyclo[6.1.0]nonene Precursors of the Bioorthogonal Reagents s-TCO and BCN. J. Org. Chem. 2018, 83, 7500-7503. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/81378 | - |
| dc.description.abstract | 近年來小分子探針工具的開發在化學生物學相關領域研究中的重要性日益增加，本論文以α-甘露醣苷酶與α-岩藻醣苷酶為對象，對其啟動式分子工具進行系統性合成策略的探討。本研究嘗試採用模組化的合成策略，以含有羥基苯甲醇/疊氮雙官能基的捕捉單元前驅物為核心架構，將複雜的合成步驟分為三個主要階段來發展具雙酬載特性的分子工具：(一)合成出全乙醯化醣苷（甘露醣與岩藻醣）連接到捕捉單元/標示部前驅物的重要中間體；（二）將第一酬載引入上述中間體的苯甲基位置；（三）去除醣苷保護基，再應用點擊化學引入第二酬載，完成下列目標化合物之合成。目標一：我們先於核心架構裡第一酬載位置引入氟原子，生成單氟甲基衍生物的捕捉機制前驅物，再藉由點擊反應在疊氮基位置分別引入螢光的發報基團（BODIPY/Cy5），完成4個α-甘露醣苷酶的活性探針分子。此探針分子庫將用於探討連接段長度以及不同螢光團對標示效能的影響。目標二：我們在捕捉機制前驅物雙酬載的位置分別引入淬滅團（BHQ2）及螢光團（Cy5）之組合，利用螢光共振轉移（FRET）的放光機制，來發展醣苷酶啟動式螢光活性探針分子。針對α-甘露醣苷酶，共完成2個此類活性探針分子，將應用於細胞顯影，來比較並驗證其效能。目標三：我們以α-岩藻醣作為辨識端，也設計了兩種探針。其一為搭配氟離去基/螢光團（BODIPY），其二為搭配淬滅團/螢光團（Dabcyl/BODIPY）之組合。我們後續也將進行一階段標示實驗，來比較此兩種螢光探針在蛋白標示上的效能。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:46:35Z (GMT). No. of bitstreams: 1 U0001-0507202114461100.pdf: 10358815 bytes, checksum: bebce56c8322f273e3ccab5d1ef50aff (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 致謝 I 摘要 II Abstract Ⅲ 圖目錄 Ⅸ 表目錄 Ⅹ 反應式目錄 ⅩI 縮寫目錄 ⅩII 第一章 緒論 1 1.1 前言........1 1.2 化學探針原理與設計......1 1.2.1 作用端...............2 1.2.2 連接橋...............2 1.2.3 發報端...............2 1.3 活性探針的應用與發展方向.............3 1.4 研究目標............................4 1.4.1 醣苷水解酶探針的發展...............4 1.4.2 應用FRET之活性探針發展.............6 1.5 論文研究目的.........................9 第二章 結果與討論 10 2.1 合成分析與討論.......................10 2.1.1 化合物8之逆合成分析................10 2.1.2 化合物8a與8b之成...................11 2.2 結論.................................14 第三章 發展α-甘露醣苷酶的含氟活性探針 15 3.1 目標分子之設計.........................15 3.1.1 化合物10a合成之設計.................16 3.1.2 α-甘露醣水解酵素對化合物10a作用情形測試................17 3.2. 化合物11a與12a合成之設計.................................19 3.3 化合物17a與18a合成之設計..................................20 3.4 α-甘露醣水解酵素對化合物11a的生物活性測試....................22 3.5 α-甘露醣水解酵素對化合物17a的生物活性測試.....................23 3.6 結論........................................................24 第四章 應用FRET分子探針之合成探討..................................25 4.1 前言..........................................................25 4.1.1 螢光共振能量轉移介紹..........................................25 4.1.2 FRET 探針作用機制..............................................25 4.1.3 螢光團及淬滅團 (quencher) 選擇介紹..............................26 4.2結合FRET之目標分子設計.............................................27 4.3 合成分析及討論....................................................28 4.3.1 化合物22a合成之探討...............................................28 4.3.2 化合物25a與28a合成之探討.........................................29 4.3.3 化合物25a與28a螢光光譜分析........................................30 4.3.4 細胞體內光學成像結果................................................33 4.4 點擊化學...............................................................34 4.4.1 BCN結構介紹..........................................................34 4.4.2 BCN衍生物合成之探討...................................................35 4.4.2.1 BCN-Cy5備...........................................................36 4.4.2.2 BCN-BODIPY製備.......................................................36 4.4.3 發展CuAAC之點擊化學......................................................36 4.4.4 連階段合成................................................................37 4.5 淬滅團之合成...............................................................38 4.5.1 BHQ2 salt合成製備........................................................38 4.5.2 Dabcyl salt合成製備......................................................39 4.6 結論.......................................................................39 第五章 以 α-岩藻醣水解酶為研究對象發展活性探針...............................41 5.1 前言.....................................................................41 5.2 實驗目的...............................................................42 5.3 合成分析與討論.............................................................43 5.3.1 化合物19b合成之探討....................................................44 5.3.2 化合物23b合成之探討.....................................................44 5.4 結論......................................................................45 第六章 總結與未來展望..........................................................46 6.1 總結...........................................................46 6.2 未來展望....................................................... 46 第七章 實驗部分..................................................................48 7.1 一般敘述....................................................................48 7.1.1 實驗儀器與測定溶劑..................................................48 7.1.2 反應試劑.....................................................................49 7.2. α-甘露醣水解酵素對化合物10a作用之實驗步驟........................49 7.3 有機合成實驗步驟及光譜數據..............................................49 參考文獻..........................................................................98 附錄..............................................................................109 | |
| dc.language.iso | zh-TW | |
| dc.subject | 點擊反應 | zh_TW |
| dc.subject | 分子探針 | zh_TW |
| dc.subject | 雙酬載 | zh_TW |
| dc.subject | 醣苷水解酶 | zh_TW |
| dc.subject | 螢光共振能量轉移 | zh_TW |
| dc.subject | dual-payload | en |
| dc.subject | click chemistry | en |
| dc.subject | activity probe | en |
| dc.subject | FRET | en |
| dc.subject | glycosidases | en |
| dc.title | 針對醣苷水解酶分子工具合成之探討 | zh_TW |
| dc.title | Synthetic effort on the development of molecular tools for glycosidases | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鄭偉杰(Hsin-Tsai Liu),吳世雄(Chih-Yang Tseng),林俊宏 | |
| dc.subject.keyword | 分子探針,雙酬載,醣苷水解酶,螢光共振能量轉移,點擊反應, | zh_TW |
| dc.subject.keyword | glycosidases,dual-payload,FRET,activity probe,click chemistry, | en |
| dc.relation.page | 159 | |
| dc.identifier.doi | 10.6342/NTU202101274 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-07-23 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| 顯示於系所單位： | 化學系 | |
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