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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 羅禮強 | zh_TW |
| dc.contributor.advisor | Lee-Chiang Lo | en |
| dc.contributor.author | 湯軒其 | zh_TW |
| dc.contributor.author | Hsuan-Chi Tang | en |
| dc.date.accessioned | 2025-02-24T16:28:33Z | - |
| dc.date.available | 2025-02-25 | - |
| dc.date.copyright | 2025-02-24 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-01-15 | - |
| dc.identifier.citation | 1. Fang, Z., & Chen, H. The in vivo drug delivery pattern of the organelle-targeting small molecules. Adv. Drug Delivery Rev., 2023, 115020.
2. Yang, J., Griffin, A., Qiang, Z., & Ren, J. Organelle-targeted therapies: a comprehensive review on system design for enabling precision oncology. Signal Transduction Targeted Ther., 2022, 7, 379. 3. Madar, I., Ravert, H., Nelkin, B., Abro, M., Pomper, M., Dannals, R., & Frost, J. J. Characterization of membrane potential-dependent uptake of the novel PET tracer 18 F-fluorobenzyl triphenylphosphonium cation. Eur. J. Nucl. Med. Mol. Imaging, 2007, 34, 2057-2065. 4. Zhang, L., Liu, W., Huang, X., Zhang, G., Wang, X., Wang, Z., ... & Jiang, X.. Old is new again: a chemical probe for targeting mitochondria and monitoring mitochondrial membrane potential in cells. Analyst, 2015, 140, 5849-5854. 5. Wang, H., Li, Y., Bai, H., Shen, J., Chen, X., Ping, Y., & Tang, G.. A cooperative dimensional strategy for enhanced nucleus‐targeted delivery of anticancer drugs. Adv. Funct. Mater., 2017, 27, 1700339. 6. Cao, Z., Li, D., Wang, J., Xiong, M., & Yang, X. Direct nucleus‐targeted drug delivery using cascade pHe/photo dual‐sensitive polymeric nanocarrier for cancer therapy. Small, 2019, 15, 1902022. 7. Tian, X., Yan, F., Zheng, J., Cui, X., Feng, L., Li, S., ... & Ma, X. Endoplasmic reticulum targeting ratiometric fluorescent probe for carboxylesterase 2 detection in drug-induced acute liver injury. Anal. Chem., 2019, 91, 15840-15845. 8. Yue, L., Huang, H., Song, W., & Lin, W. A near-infrared endoplasmic reticulum-targeted fluorescent probe to visualize the fluctuation of SO2 during endoplasmic reticulum stress. Chem. Eng. J., 2022, 431, 133468. 9. Hu, Y. B., Dammer, E. B., Ren, R. J., & Wang, G. The endosomal-lysosomal system: from acidification and cargo sorting to neurodegeneration. Transl. Neurodegener., 2015, 4, 1-10. 10. Castino, R., Démoz, M., & Isidoro, C. Destination ‘lysosome’: a target organelle for tumour cell killing?. J. Mol. Recognit., 2003, 16, 337-348. 11. Concolino, D., Deodato, F., & Parini, R. Enzyme replacement therapy: efficacy and limitations. Ital. J. Pediatr., 2018, 44, 117-126. 12. Zhu, Y., Jiang, J. L., Gumlaw, N. K., Zhang, J., Bercury, S. D., Ziegler, R. J., ... & Cheng, S. H. Glycoengineered acid α-glucosidase with improved efficacy at correcting the metabolic aberrations and motor function deficits in a mouse model of Pompe disease. Mol. Ther., 2009, 17, 954-963. 13. Mondal, B., Dutta, T., Padhy, A., Das, S., & Sen Gupta, S. Lysosome-targeting strategy using polypeptides and chimeric molecules. ACS omega, 2021, 7, 5-16. 14. Gauthier, C., El Cheikh, K., Basile, I., Daurat, M., Morère, E., Garcia, M., ... & Gary-Bobo, M. Cation-independent mannose 6-phosphate receptor: From roles and functions to targeted therapies. J. Controlled Release, 2024, 365, 759-772. 15. Gary-Bobo, M., Nirdé, P., Jeanjean, A., Morère, A., & Garcia, M. Mannose 6-phosphate receptor targeting and its applications in human diseases. Curr. Med. Chem., 2007, 14, 2945-2953. 16. Kornfeld, S. Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors. Annu. Rev. Biochem., 1992, 61, 307-330. 17. Jeanjean, A., Garcia, M., Leydet, A., Montero, J. L., & Morère, A. Synthesis and receptor binding affinity of carboxylate analogues of the mannose 6-phosphate recognition marker. Bioorg. Med. Chem., 2006, 14, 3575-3582. 18. Foret, J., de Courcy, B., Gresh, N., Piquemal, J. P., & Salmon, L. Synthesis and evaluation of non-hydrolyzable D-mannose 6-phosphate surrogates reveal 6-deoxy-6-dicarboxymethyl-D-mannose as a new strong inhibitor of phosphomannose isomerases. Bioorg. Med. Chem., 2009, 17, 7100-7107. 19. Barragan-Montero, V., Awwad, A., Combemale, S., de Santa Barbara, P., Jover, B., Mols, J. P., & Montero, J. L. Synthesis of Mannose-6-Phosphate analogues and their utility as angiogenesis regulators. ChemMedChem., 2011, 6, 1771 – 1774. 20. Clavel, C., Barragan-Montero, V., Garric, X., Molès, J. P., & Montero, J. L. Synthesis and biological activity of M6-P and M6-P analogs on fibroblast and keratinocyte proliferation. Il Farmaco, 2005, 60, 721-725. 21. Banik, S. M., Pedram, K., Wisnovsky, S., Ahn, G., Riley, N. M., & Bertozzi, C. R. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature, 2020, 584, 291-297. 22. Jeanjean, A., Gary-Bobo, M., Nirdé, P., Leiris, S., Garcia, M., & Morère, A. Synthesis of new sulfonate and phosphonate derivatives for cation-independent mannose 6-phosphate receptor targeting. Bioorg. Med. Chem. Lett., 2008, 18, 6240-6243. 23. Basile, I., Da Silva, A., El Cheikh, K., Godefroy, A., Daurat, M., Harmois, A., ... & Maynadier, M. Efficient therapy for refractory Pompe disease by mannose 6-phosphate analogue grafting on acid α-glucosidase. J. Controlled Release, 2018, 269, 15-23. 24. Tong, P. Y., Gregory, W., & Kornfeld, S. Ligand interactions of the cation-independent mannose 6-phosphate receptor: the stoichiometry of mannose 6-phosphate binding. J. Biol. Chem., 1989, 264, 7962-7969. 25. Desnick, R. J., & Schuchman, E. H. Enzyme replacement and enhancement therapies: lessons from lysosomal disorders. Nat. Rev. Genet., 2002, 3, 954-966. 26. Stirnemann, J., Belmatoug, N., Camou, F., Serratrice, C., Froissart, R., Caillaud, C., ... & Berger, M. G. A review of Gaucher disease pathophysiology, clinical presentation and treatments. Int. J. Mol. Sci., 2017, 18, 441. 27. Hollak, C. E., & Wijburg, F. A. Treatment of lysosomal storage disorders: successes and challenges. J. Inherited Metab. Dis., 2014, 37, 587-598. 28. Oh, D. B. Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases. BMB Rep., 2015, 48, 438. 29. Kang, J. Y., Shin, K. K., Kim, H. H., Min, J. K., Ji, E. S., Kim, J. Y., ... & Oh, D. B. Lysosomal targeting enhancement by conjugation of glycopeptides containing mannose-6-phosphate glycans derived from glyco-engineered yeast. Sci. Rep., 2018, 8, 8730. 30. Zhu, Y., Li, X., Mcvie-Wylie, A., Jiang, C., Thurberg, B. L., Raben, N., ... & Cheng, S. H. Carbohydrate-remodelled acid α-glucosidase with higher affinity for the cation-independent mannose 6-phosphate receptor demonstrates improved delivery to muscles of Pompe mice. Biochem. J., 2005, 389, 619-628 31. El Cheikh, K., Basile, I., Da Silva, A., Bernon, C., Cérutti, P., Salgues, F., ... & Morère, A. Design of potent mannose 6‐phosphate analogues for the functionalization of lysosomal enzymes to improve the treatment of pompe disease. Angew. Chem., Int. Ed., 2016, 55, 14774-14777. 32. Togawa, T., Takada, M., Aizawa, Y., Tsukimura, T., Chiba, Y., & Sakuraba, H. Comparative study on mannose 6-phosphate residue contents of recombinant lysosomal enzymes. Mol. Genet. Metab., 2014, 111, 369-373. 33. McVie-Wylie, A. J., Lee, K. L., Qiu, H., Jin, X., Do, H., Gotschall, R., ... & Mattaliano, R. J.. Biochemical and pharmacological characterization of different recombinant acid α-glucosidase preparations evaluated for the treatment of Pompe disease. Mol. Genet. Metab., 2008, 94, 448-455. 34. Xiao, H., Chen, W., Smeekens, J. M., & Wu, R. An enrichment method based on synergistic and reversible covalent interactions for large-scale analysis of glycoproteins. Nat. Commun., 2018, 9, 1692. 35. Zhou, Y., Teng, P., Montgomery, N. T., Li, X., & Tang, W. Development of triantennary N-acetylgalactosamine conjugates as degraders for extracellular proteins. ACS Cent. Sci., 2021, 7, 499-506. 36. Sattin, S., Daghetti, A., Thepaut, M., Berzi, A., Sanchez-Navarro, M., Tabarani, G., ... & Bernardi, A. Inhibition of DC-SIGN-mediated HIV infection by a linear trimannoside mimic in a tetravalent presentation. ACS Chem. Biol., 2010, 5, 301-312. 37. Wu, P., Malkoch, M., Hunt, J. N., Vestberg, R., Kaltgrad, E., Finn, M. G., ... & Hawker, C. J. Multivalent, bifunctional dendrimers prepared by click chemistry. Chem. Commun., 2005, 46, 5775-5777. 38. Zheng, T., Rouhanifard, S. H., Jalloh, A. S., & Wu, P. Click triazoles for bioconjugation. Click triazoles, 2012, 163-183. 39. Khandelwal, R., Vasava, M., Abhirami, R. B., & Karsharma, M. Recent advances in triazole synthesis via click chemistry and their pharmacological applications: A review. Bioorg. Med. Chem. Lett., 2024, 129927. 40. 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., 2002, 114, 2708-2711. 41. Sletten, E. M., & Bertozzi, C. R. From mechanism to mouse: a tale of two bioorthogonal reactions. Acc. Chem. Res., 2011, 44, 666-676. 42.Singh, G., Singh, R., Singh, G., Stanzin, J., Singh, H., Kaur, G., & Singh, J. Clicking in harmony: exploring the bio-orthogonal overlap in click chemistry. RSC Adv., 2024, 14, 7383-7413. 43. Geng, Z., Shin, J. J., Xi, Y., & Hawker, C. J. Click chemistry strategies for the accelerated synthesis of functional macromolecules. J. Polym. Sci., 2021, 59, 963-1042. 44. Boutureira, O., & Bernardes, G. J. Advances in chemical protein modification. Chem. Rev., 2015, 115, 2174-2195. 45. Gennari, A., Wedgwood, J., Lallana, E., Francini, N., & Tirelli, N. (2020). Thiol-based michael-type addition. A systematic evaluation of its controlling factors. Tetrahedron, 2020, 76, 131637. 46. Kim, J., Choi, Y., Park, J., Lee, H. Y., & Choi, J. Peptides conjugation on biomaterials: chemical conjugation approaches and their promoted multifunction for biomedical applications. Biotechnol. Bioprocess Eng., 2024, 29, 427-439. 47. Nair, D. P., Podgorski, M., Chatani, S., Gong, T., Xi, W., Fenoli, C. R., & Bowman, C. N. The thiol-Michael addition click reaction: a powerful and widely used tool in materials chemistry. Chem. Mater., 2014, 26, 724-744. 48. Khanjin, N. A., & Montero, J. L. Synthesis of mannose-6-phosphate analogs: Large-scale preparation of isosteric mannose-6-phosphonate via cyclic sulfate precursor. Tetrahedron Lett., 2002, 43, 4017-4020. 49. Han, X., Alameh, M. G., Gong, N., Xue, L., Ghattas, M., Bojja, G., ... & Mitchell, M. J. (2024). Fast and facile synthesis of amidine-incorporated degradable lipids for versatile mRNA delivery in vivo. Nat. Chem., 2024, 16, 1687-1697. 50. Wilson, D. S., Hirosue, S., Raczy, M. M., Bonilla-Ramirez, L., Jeanbart, L., Wang, R., ... & Hubbell, J. A. Antigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunity. Nat. Mater., 2019, 18, 175-185. 51. Espeel, P., Goethals, F., Driessen, F., Nguyen, L. T. T., & Du Prez, F. E. One-pot, additive-free preparation of functionalized polyurethanes via amine–thiol–ene conjugation. Polym. Chem., 2013, 4, 2449-2456. 52. Kurowska, I., Amouroux, B., Langlais, M., Coutelier, O., Coudret, C., Destarac, M., & Marty, J. D. Versatile thiolactone-based conjugation strategies to polymer stabilizers for multifunctional upconverting nanoparticles aqueous dispersions. Nanoscale, 2022, 14, 2238-2247. 53. Combemale, S., Assam-Evoung, J. N., Houaidji, S., Bibi, R., & Barragan-Montero, V. Gold nanoparticles decorated with mannose-6-phosphate analogues. Molecules, 2014, 19, 1120-1149. 54. Warneke, J., Wang, Z., Zeller, M., Leibfritz, D., Plaumann, M., & Azov, V. A. Methacryloyl chloride dimers: from structure elucidation to a manifold of chemical transformations. Tetrahedron, 2014, 70, 6515-6521. 55. Chiminelli, M., Scarica, G., Balestri, D., Marchiò, L., Della Ca, N., & Maestri, G. The visible-light-promoted intermolecular para-cycloadditions of allenamides on naphthalene. Tetrahedron Chem, 2023, 8, 100053. 56. Derkaoui, S., Belbachir, M., Haoue, S., Zeggai, F. Z., Rahmouni, A., & Ayat, M.. Homopolymerization of methacrylamide by anionic process under effect of Maghnite-Na+ (Algerian MMT). J. Organomet. Chem., 2019, 893, 52-60. 57. Chabre, Y. M., Contino-Pépin, C., Placide, V., Shiao, T. C., & Roy, R. Expeditive synthesis of glycodendrimer scaffolds based on versatile TRIS and mannoside derivatives. The Journal of organic chemistry, 2008, 73, 5602-5605. 58. Li, C. W., Hon, K. W., Ghosh, B., Li, P. H., Lin, H. Y., Chan, P. H., ... & Mong, K. K. T. Synthesis of oligomeric mannosides and their structure‐binding relationship with concanavalin A. Chemistry–An Asian Journal, 2014, 9, 1786-1796. 59. Riddles, P. W., Blakeley, R. L., & Zerner, B. Reassessment of Ellman's reagent. In Methods in enzymology, 1983, 91, 49-60. 60. Wilson, D. S., Hirosue, S., Raczy, M. M., Bonilla-Ramirez, L., Jeanbart, L., Wang, R., ... & Hubbell, J. A. Antigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunity. Nat. Mater., 2019, 18, 175-185. 61. Lin, Y., Gao, J. W., Liu, H. W., & Li, Y. S. Synthesis and characterization of hyperbranched poly (ether amide) s with thermoresponsive property and unexpected strong blue photoluminescence. Macromolecules, 2009, 42, 3237-3246. 62. Sattin, S., Daghetti, A., Thepaut, M., Berzi, A., Sanchez-Navarro, M., Tabarani, G., ... & Bernardi, A. Inhibition of DC-SIGN-mediated HIV infection by a linear trimannoside mimic in a tetravalent presentation. ACS Chem. Biol., 2010, 5, 301-312. 63. Collet, C., Maskali, F., Clément, A., Chrétien, F., Poussier, S., Karcher, G., ... & Lamandé‐Langle, S. Development of 6‐[18F] fluoro‐carbohydrate‐based prosthetic groups and their conjugation to peptides via click chemistry. J. Labelled Compd. Radiopharm., 2016, 59, 54-62. 64. Lippincott, D. J., Linstadt, R. T., Maser, M. R., Gallou, F., & Lipshutz, B. H. Synthesis of functionalized 1, 3-butadienes via Pd-catalyzed cross-couplings of substituted allenic esters in water at room temperature. Org. Lett., 2018, 20, 4719-4722. 65. Gulati, H. K.; Choudhary, S.; Kumar, N.; Ahmed, A.; Bhagat, K.; Singh, J. V.; Mukherjee, D. Design, Synthesis, biological investigations and molecular interactions of triazole linked tacrine glycoconjugates as Acetylcholinesterase inhibitors with reduced hepatotoxicity. Bioorg. Chem., 2022, 118, 105479. 66. Liu, L. J.; Yoo, J. C.; Hong, J. H. Efficient synthesis of 4′-cyclopropylated carbovir analogues with use of ring-closing metathesis from glycolate. Nucleosides, Nucleotides and Nucleic Acids, 2008, 27, 1186-1196. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/96901 | - |
| dc.description.abstract | 甘露醣-6-磷酸 (Mannose-6-Phosphate, M6P) 是一種生物體內存在的重要辨識標記物，當其與甘露醣-6-磷酸受體結合後，酸性水解酶會被運輸至溶酶體，並將細胞內多餘的大分子分解進行回收利用；然而，當其中一種水解酶突變導致溶酶體功能異常時，會使大分子堆積在細胞中造成細胞死亡，這一種罕見遺傳性疾病稱為溶酶體儲積症 (Lysosomal Storage Disorders, LSDs)。目前針對此類疾病的主要治療方法為酵素替代療法 (Enzyme Replacement Therapy, ERT)，意即將缺乏的酵素透過外部生產的方式送至細胞內，以維持細胞正常運作。因此，通過化學修飾將 M6P 結合至酵素，以提升療效，已成為相關研究的熱門主題。
本研究首先嘗試合成具有疊氮基團 (N3) 的 M6P 衍生物，將天然物 M6P 中 6 號位的磷酸根改為較不易水解的丙二酸根 (malonate)，據文獻指出其不但能提升與受體的結合能力，同時具有較不易水解的特性；另外在 1 號位引入疊氮基團，能再透過點擊化學連接具炔鍵的結構，大幅提升其後續發展性。 接著則著重於設計能進行點擊反應之多種連接段，希望透過點擊反應快速合成單價及三價且具有不同麥可受體 (michael acceptor) 之分子工具，並初步測試其與硫醇的反應性，以挑選最適合與酵素結合的化合物。期望未來能將這些化合物結合目標水解酶，在不影響水解酶活性的前提下，提升酵素中 M6P 之含量，進一步改善酵素替代療法之效能。 | zh_TW |
| dc.description.abstract | Mannose-6-Phosphate (M6P) is an essential recognition marker found in biological systems. When M6P binds to the Mannose-6-Phosphate Receptor (M6PR), acidic hydrolases will be transported to the lysosome, where they degrade excess macromolecules within the cell for recycling. However, when one of these hydrolases is defective due to mutations, it will lead to the accumulation of macromolecules within the cell and ultimately resulting in cell death. This rare disease is known as Lysosomal Storage Disorder (LSDs). The current primary treatment for LSDs is Enzyme Replacement Therapy (ERT), which involves delivering externally produced enzymes into cells to maintain normal cellular functions. Consequently, chemically modifying M6P to enhance its binding to enzymes and improve therapeutic efficacy has become a prominent research focus.
This study aims to synthesize M6P derivatives containing an azido group (N₃). Specifically, the phosphate group at the 6-position of natural M6P is replaced with a more hydrolysis-resistant malonate group. According to the literature, this modification not only enhances the binding affinity to the receptor but also improves stability. Additionally, introducing an azido group at the 1-position enables further functionalization through click chemistry with alkyne-containing compounds, significantly broadening its potential applications. This research then focuses on designing various linkers compatible with click reactions to rapidly synthesize monovalent and trivalent molecular tools containing different michael acceptors. These tools are subjected to preliminary reactivity tests with thiols to identify the most suitable compound for enzyme conjugation. It is anticipated that these compounds can be conjugated to target hydrolases, increasing the M6P content in enzymes while preserving their catalytic activity. This approach aims to further enhance the efficacy of enzyme replacement therapy. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-02-24T16:28:33Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-02-24T16:28:33Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 中文摘要 I
Abstract II 圖次 VI 表次 VIII 反應式目錄 IX 縮寫目錄 XI 第一章 緒論 1 1-1. 前言 1 1-2. 溶酶體與甘露醣-6-磷酸受體 2 1-3. 甘露醣-6-磷酸及其衍生物 4 1-4. 溶小體儲積症與酵素替代療法 8 1-5. 甘露醣-6-磷酸衍生物進行酵素替代療法之相關研究 9 1-6. 研究動機與方向 14 1-6-1. 具有疊氮基團的甘露醣-6-磷酸衍生物之設計與規劃 15 1-6-2. 以點擊反應開發多價結構之探討 16 1-6-3. 酵素修飾以及連接端 (connector) 之設計探討 17 1-6-4. 多價樹枝狀結構之設計 19 第二章 結果與討論 22 2-1. 甘露醣-6-磷酸衍生物 16 的設計與合成 22 2-1-1. α-Mannose azide-化合物 7 之合成分析 23 2-1-2. 化合物 9 (含對甲苯磺醯基離去基) 的合成與反應性探討 24 2-1-3. 化合物 13 (cyclic sulfate結構) 的合成與反應性探討 26 2-1-4. 化合物 14 的去保護及水解反應順序探討 27 2-1-5. 化合物 36 (含三氟甲磺醯基離去基) 的合成與反應性探討 30 2-2. 單價甘露醣-6-磷酸目標物 33 及 39 的設計與合成探討 32 2-2-1. 化合物 31 的合成與探討 33 2-2-2. 化合物 33 之合成探討與光譜分析 34 2-2-3. 化合物 39 的合成與探討 36 2-3. 三價甘露醣-6-磷酸 30 目標物的設計與合成探討 37 2-3-1. 化合物 28 的合成探討 39 2-3-2. 與化合物 16 進行點擊反應合成化合物 30 之探討 40 2-3-3. 與化合物 15 進行點擊反應合成化合物 30 之探討 41 2-4. 三價甘露醣-6-磷酸目標物 46 的設計與合成探討 43 2-4-1. 化合物 42 及 45的合成探討 44 2-4-2. 化合物 43 的合成探討 45 2-4-3. 化合物 46 的合成探討 46 2-5. 甘露醣-6-磷酸衍生物與含硫醇胺基酸之結合測試 47 2-5-1. 以 HPLC 及 UV-VIS 追蹤化合物 33 及 39 與麩胱甘肽之反應情形 48 2-5-2. 以 HPLC 及 UV-VIS 追蹤化合物 39 與不同硫醇之反應情形 53 2-5-3. 以 UV-VIS 追蹤化合物 39 及46 與乙醯半胱胺酸之反應情形 56 2-6. 結論 58 第三章 實驗部分 59 3-1. 一般敘述 59 3-2. 反應試劑 60 3-3. 有機合成實驗步驟及光譜數據 61 參考文獻 82 附錄 94 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 設計與開發以麥可加成應用於蛋白質修飾之功能性連接段 | zh_TW |
| dc.title | Design and Development of Functional Linkers for Protein Modification via Michael Addition | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 鄭偉杰;高佳麟 | zh_TW |
| dc.contributor.oralexamcommittee | Wei-Chieh Cheng ;Chai-Lin Kao | en |
| dc.subject.keyword | 甘露醣-6-磷酸,酵素替代療法,點擊反應,麥可加成反應, | zh_TW |
| dc.subject.keyword | Mannose-6-Phosphate,Enzyme Replacement Therapy,click reaction,michael addition reaction, | en |
| dc.relation.page | 116 | - |
| dc.identifier.doi | 10.6342/NTU202500123 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-01-16 | - |
| dc.contributor.author-college | 理學院 | - |
| dc.contributor.author-dept | 化學系 | - |
| dc.date.embargo-lift | N/A | - |
| 顯示於系所單位： | 化學系 | |
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