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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/96618完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王宗興 | zh_TW |
| dc.contributor.advisor | Tsung-Shing Andrew Wang | en |
| dc.contributor.author | 高志堯 | zh_TW |
| dc.contributor.author | Chih-Yao Kao | en |
| dc.date.accessioned | 2025-02-20T16:13:46Z | - |
| dc.date.available | 2025-02-21 | - |
| dc.date.copyright | 2025-02-20 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-01-21 | - |
| dc.identifier.citation | (1) Wu, X.; Li, Z.; Chen, X. X.; Fossey, J. S.; James, T. D.; Jiang, Y. B. Selective sensing of saccharides using simple boronic acids and their aggregates. Chem. Soc. Rev. 2013, 42(20), 8032-8048.
(2) Akgun, B.; Hall, D. G. Boronic acids as bioorthogonal probes for site-selective labeling of proteins. Angew. Chem. Int. Ed. 2018, 57(40), 13028-13044. (3) Antonio, J. P. M.; Russo, R.; Carvalho, C. P.; Cal, P.; Gois, P. M. P. Boronic acids as building blocks for the construction of therapeutically useful bioconjugates. Chem. Soc. Rev. 2019, 48(13), 3513-3536. (4) Williams, G. T.; Kedge, J. L.; Fossey, J. S. Molecular boronic acid-based saccharide sensors. ACS Sens. 2021, 6(4), 1508-1528. (5) Yang, W.; Gao, X.; Wang, B. Boronic acid compounds as potential pharmaceutical agents. Med. Res. Rev. 2003, 23(3), 346-368. (6) Trippier, P. C.; McGuigan, C. Boronic acids in medicinal chemistry: anticancer, antibacterial and antiviral applications. MedChemComm. 2010, 1(3), 183-198. (7) Baker, S. J.; Tomsho, J. W.; Benkovic, S. J. Boron-containing inhibitors of synthetases. Chem. Soc. Rev. 2011, 40(8), 4279-4285. (8) Plescia, J.; Moitessier, N. Design and discovery of boronic acid drugs. Eur. J. Med. Chem. 2020, 195, 112270. (9) Malouff, T. D.; Seneviratne, D. S.; Ebner, D. K.; Stross, W. C.; Waddle, M. R.; Trifiletti, D. M.; Krishnan, S. Boron neutron capture therapy: a review of clinical applications. Front. Oncol. 2021, 11, 601820. (10) Nishikawa, M.; Kang, H. G.; Zou, Y.; Takeuchi, H.; Matsuno, N.; Suzuki, M.; Komatsu, N. Conjugation of phenylboronic acid moiety through multistep organic transformations on nanodiamond surface for an anticancer nanodrug for boron neutron capture therapy. Bull. Chem. Soc. Jpn. 2021, 94(9), 2302-2312. (11) Kim, A.; Suzuki, M.; Matsumoto, Y.; Fukumitsu, N.; Nagasaki, Y. Non-isotope enriched phenylboronic acid-decorated dual-functional nano-assembles for an actively targeting BNCT drug. Biomaterials 2021, 268, 120551. (12) Schauenburg, D.; Gao, B.; Rochet, L. N. C.; Schuler, D.; Coelho, J. A. S.; Ng, D. Y. W.; Chudasama, V.; Kuan, S. L.; Weil, T. Macrocyclic dual-locked "turn-on" drug for selective and traceless release in cancer cells. Angew. Chem. Int. Ed. 2024, 63(18), e202314143. (13) Sufian, A.; Bhattacherjee, D.; Mishra, T.; Bhabak, K. P. Peroxide-responsive boronate ester-coupled turn-on fluorogenic probes: Direct linkers supersede self-immolative linkers for sensing peroxides. Dyes Pigm. 2021, 191, 109363. (14) Stubelius, A.; Lee, S.; Almutairi, A. The chemistry of boronic acids in nanomaterials for drug delivery. Acc. Chem. Res. 2019, 52(11), 3108-3119. (15) Stephenson-Brown, A.; Yong, S.; Mansor, M. H.; Hussein, Z.; Yip, N. C.; Mendes, P. M.; Fossey, J. S.; Rawson, F. J. Electronic communication of cells with a surface mediated by boronic acid saccharide interactions. Chem. Commun. 2015, 51(97), 17213-17216. (16) Sun, X.; Zhai, W.; Fossey, J. S.; James, T. D. Boronic acids for fluorescence imaging of carbohydrates. Chem. Commun. 2016, 52(17), 3456-3469. (17) Jabbour, A.; Steinberg, D.; Dembitsky, V. M.; Moussaieff, A.; Zaks, B.; Srebnik, M. Synthesis and evaluation of oxazaborolidines for antibacterial activity against Streptococcus mutans. J. Med. Chem. 2004, 47(10), 2409-2410. (18) Kim, A.; Suzuki, Y.; Nagasaki, Y. Molecular design of a high-performance polymeric carrier for delivery of a variety of boronic acid-containing drugs. Acta Biomater. 2021, 121, 554-565. (19) Vargas, R. D.; Ding, Y.; Trial, H. O.; Qian, R.; Ball, Z. T. Polyol recognition in catalysis: toward selective modification of glycosylated polypeptides with boronic acid-rhodium(II) catalysts. Chem. Commun. 2023, 59(87), 13030-13033. (20) Banach, Ł.; Williams, G. T.; Fossey, J. S. Insulin delivery using dynamic covalent boronic acid/ester‐controlled release. Adv. Therap. 2021, 4(11), 2100118. (21) Liu, H.; Li, Y.; Sun, K.; Fan, J.; Zhang, P.; Meng, J.; Wang, S.; Jiang, L. Dual-responsive surfaces modified with phenylboronic acid-containing polymer brush to reversibly capture and release cancer cells. J. Am. Chem. Soc. 2013, 135(20), 7603-7609. (22) Yan, J.; Springsteen, G.; Deeter, S.; Wang, B. The relationship among pKa, pH, and binding constants in the interactions between boronic acids and diols—it is not as simple as it appears. Tetrahedron 2004, 60(49), 11205-11209. (23) Zhao, D.; Xu, J. Q.; Yi, X. Q.; Zhang, Q.; Cheng, S. X.; Zhuo, R. X.; Li, F. pH-Activated targeting drug delivery system based on the selective binding of phenylboronic acid. ACS Appl. Mater. Interfaces 2016, 8(23), 14845-14854. (24) Zhu, J.; Huo, Q.; Xu, M.; Yang, F.; Li, Y.; Shi, H.; Niu, Y.; Liu, Y. Bortezomib-catechol conjugated prodrug micelles: combining bone targeting and aryl boronate-based pH-responsive drug release for cancer bone-metastasis therapy. Nanoscale 2018, 10(38), 18387-18397. (25) Kane, R. C.; Farrell, A. T.; Sridhara, R.; Pazdur, R. United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clin. Cancer Res. 2006, 12(10), 2955-2960. (26) Groll, M.; Berkers, C. R.; Ploegh, H. L.; Ovaa, H. Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome. Structure 2006, 14(3), 451-456. (27) Chen, D.; Frezza, M.; Schmitt, S.; Kanwar, J.; P Dou, Q. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr. Cancer Drug Targets 2011, 11(3), 239-253. (28) Shirley, M. Ixazomib: First Global Approval. Drugs 2016, 76(3), 405-411. (29) Muz, B.; Ghazarian, R. N.; Ou, M.; Luderer, M. J.; Kusdono, H. D.; Azab, A. K. Spotlight on ixazomib: potential in the treatment of multiple myeloma. Drug Des. Devel. Ther. 2016, 10, 217-226. (30) Baker, S. J.; Zhang, Y. K.; Akama, T.; Lau, A.; Zhou, H.; Hernandez, V.; Plattner, J. J. Discovery of a new boron-containing antifungal agent, 5-fluoro-1, 3-dihydro-1-hydroxy-2, 1-benzoxaborole (AN2690), for the potential treatment of onychomycosis. J. Med. Chem. 2006, 49(15), 4447-4450. (31) Jinna, S.; Finch, J. Spotlight on tavaborole for the treatment of onychomycosis. Drug Des. Devel. Ther. 2015, 9, 6185-6190. (32) Akama, T.; Baker, S. J.; Zhang, Y. K.; Hernandez, V.; Zhou, H.; Sanders, V.; Freund, Y.; Kimura, R.; Maples, K. R.; Plattner, J. J. Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg. Med. Chem. Lett. 2009, 19(8), 2129-2132. (33) Livermore, D. M.; Mushtaq, S. Activity of biapenem (RPX2003) combined with the boronate beta-lactamase inhibitor RPX7009 against carbapenem-resistant Enterobacteriaceae. J. Antimicrob. Chemother. 2013, 68(8), 1825-1831. (34) Yang, W.; Gao, X.; Wang, B. Boronic acid compounds as potential pharmaceutical agents. Med. Res. Rev. 2003, 23(3), 346-368. (35) Springsteen, G.; Wang, B. A detailed examination of boronic acid–diol complexation. Tetrahedron 2002, 58(26), 5291-5300. (36) Bachelier, N.; Verchere, J. F. Formation of neutral complexes of boric acid with 1, 3-diols in organic solvents and in aqueous solution. Polyhedron 1995, 14(13-14), 2009-2017. (37) Halo, T. L.; Appelbaum, J.; Hobert, E. M.; Balkin, D. M.; Schepartz, A. Selective recognition of protein tetraserine motifs with a cell-permeable, pro-fluorescent bis-boronic acid. J. Am. Chem. Soc. 2009, 131(2), 438-439. (38) Akgun, B.; Hall, D. G. Fast and tight boronate formation for click bioorthogonal conjugation. Angew. Chem. Int. Ed. 2016, 55(12), 3909-3913. (39) Akgun, B.; Li, C.; Hao, Y.; Lambkin, G.; Derda, R.; Hall, D. G. Synergic "click" boronate/thiosemicarbazone system for fast and irreversible bioorthogonal conjugation in live cells. J. Am. Chem. Soc. 2017, 139(40), 14285-14291. (40) Mokrani, S.; Saidi, M. Current advances in diabetes type 1 and type 2 treatment: An overview. J. Diabetes Metab. Disord. 2020, 5, 111–114. (41) Xie, B.; Wang, K.; Li, B.; Huang, R.; Xu, Z.; Li, X. Biomaterial-mediated strategies for accurate and convenient diagnosis, and effective treatment of diabetes: advantages, current progress and future perspectives. J. Mater. Chem. B 2023, 11(17), 3766-3786. (42) Hassan, M. H.; Vyas, C.; Grieve, B.; Bartolo, P. Recent advances in enzymatic and non-enzymatic electrochemical glucose sensing. Sensors (Basel) 2021, 21(14), 4672. (43) Mohamad Nor, N.; Ridhuan, N. S.; Abdul Razak, K. Progress of enzymatic and non- enzymatic electrochemical glucose biosensor based on nanomaterial-modified electrode. Biosensors (Basel) 2022, 12(12), 1136. (44) Nan, K.; Jiang, Y. N.; Li, M.; Wang, B. Recent progress in diboronic-acid-based glucose sensors. Biosensors (Basel) 2023, 13(6), 618. (45) James, T. D.; Sandanayake, K. R. A. S.; Shinkai, S. A glucose‐selective molecular fluorescence sensor. Angew. Chem. Int. Ed. Engl. 1994, 33(21), 2207-2209. (46) James, T.D.; Shinmori, H.; Shinkai, S. Novel fluorescence sensor for ‘small’ saccharides. Chem. Commun. 1997, 1, 71–72. (47) Arimori, S.; Bell, M. L.; Oh, C. S.; Frimat, K. A.; James, T. D. Modular fluorescence sensors for saccharides. J. Chem. Soc., Dalton Trans. 2002, 6, 803-808. (48) Sun, X.; Chapin, B. M.; Metola, P.; Collins, B.; Wang, B.; James, T. D.; Anslyn, E. V. The mechanisms of boronate ester formation and fluorescent turn-on in ortho-aminomethylphenylboronic acids. Nat. Chem. 2019, 11(9), 768-778. (49) Kropff, J.; Choudhary, P.; Neupane, S.; Barnard, K.; Bain, S. C.; Kapitza, C.; Forst, T.; Link, M.; Dehennis, A.; DeVries, J. H. Accuracy and longevity of an implantable continuous glucose sensor in the PRECISE study: A 180-Day, Prospective, Multicenter, Pivotal Trial. Diabetes Care 2017, 40(1), 63-68. (50) Joseph, J. I. Review of the long-term implantable senseonics continuous glucose monitoring system and other continuous glucose monitoring systems. J. Diabetes Sci. Technol. 2021, 15(1), 167-173. (51) Garg, S. K.; Liljenquist, D.; Bode, B.; Christiansen, M. P.; Bailey, T. S.; Brazg, R. L.; Denham, D. S.; Chang, A. R.; Akturk, H. K.; Dehennis, A.; Tweden, K. S.; Kaufman, F. R. Evaluation of accuracy and safety of the next-generation up to 180-day long-term implantable eversense continuous glucose monitoring system: the promise study. Diabetes Technol. Ther. 2022, 24(2), 84-92. (52) Irace, C.; Cutruzzola, A.; Tweden, K.; Kaufman, F. R. Device profile of the eversense continuous glucose monitoring system for glycemic control in type-1 diabetes: overview of its safety and efficacy. Expert Rev. Med. Devices 2021, 18(10), 909-914. (53) Suzuki, Y.; Mizuta, Y.; Mikagi, A.; Misawa-Suzuki, T.; Tsuchido, Y.; Sugaya, T.; Hashimoto, T.; Ema, K.; Hayashita, T. Recognition of D-glucose in water with excellent sensitivity, selectivity, and chiral selectivity using gamma-cyclodextrin and fluorescent boronic acid inclusion complexes having a pseudo-diboronic acid moiety. ACS Sens. 2023, 8(1), 218-227. (54) Wang, K.; Zhang, R.; Yue, X.; Zhou, Z.; Bai, L.; Tong, Y.; Wang, B.; Gu, D.; Wang, S.; Qiao, Y.; Liu, Q.; Xue, X.; Yin, Y.; Xi, R.; Meng, M. Synthesis of diboronic acid-based fluorescent probes for the sensitive detection of glucose in aqueous media and biological matrices. ACS Sens. 2021, 6(4), 1543-1551. (55) Tommasone, S.; Allabush, F.; Tagger, Y. K.; Norman, J.; Köpf, M.; Tucker, J. H.; Mendes, P. M. The challenges of glycan recognition with natural and artificial receptors. Chem. Soc. Rev. 2019, 48(22), 5488-5505. (56) Wang, K.; Zhang, R.; Zhao, X.; Ma, Y.; Ren, L.; Ren, Y.; Chen, G.; Ye, D.; Wu, J.; Hu, X. Reversible recognition-based boronic acid probes for glucose detection in live cells and zebrafish. J. Am. Chem. Soc. 2023, 145(15), 8408-8416. (57) Kitano, S.; Koyama, Y.; Kataoka, K.; Okano, T.; Sakurai, Y. A novel drug delivery system utilizing a glucose responsive polymer complex between poly (vinyl alcohol) and poly (N-vinyl-2-pyrrolidone) with a phenylboronic acid moiety. J. Control. Release 1992, 19(1-3), 161-170. (58) Wang, L.; Xie, S.; Ma, L.; Chen, Y.; Lu, W. 10-Boronic acid substituted camptothecin as prodrug of SN-38. Eur. J. Med. Chem. 2016, 116, 84-89. (59) Du, L.; Li, M.; Zheng, S.; Wang, B. Rational design of a fluorescent hydrogen peroxide probe based on the umbelliferone fluorophore. Tetrahedron Lett. 2008, 49(19), 3045-3048. (60) Roy, C. D.; Brown, H. C. A comparative study of the relative stability of representative chiral and achiral boronic esters employing transesterification. Monatsh. Chem. 2007, 138(9), 879-887. (61) Bernardini, R.; Oliva, A.; Paganelli, A.; Menta, E.; Grugni, M.; Munari, S. D.; Goldoni, L. Stability of boronic esters to hydrolysis: a comparative study. Chem. Lett. 2009, 38(7), 750-751. (62) Brooks, W. L. A.; Deng, C. C.; Sumerlin, B. S. Structure-reactivity relationships in boronic acid-diol complexation. ACS Omega 2018, 3(12), 17863-17870. (63) Martinez-Aguirre, M. A.; Flores-Alamo, M.; Medrano, F.; Yatsimirsky, A. K. Examination of pinanediol-boronic acid ester formation in aqueous media: relevance to the relative stability of trigonal and tetrahedral boronate esters. Org. Biomol. Chem. 2020, 18(14), 2716-2726. (64) Gavriel, A. G.; Sambrook, M. R.; Russell, A. T.; Hayes, W. Recent advances in self- immolative linkers and their applications in polymeric reporting systems. Polym. Chem. 2022, 13(22), 3188-3269. (65) Shao, Q.; Jiang, T.; Ren, G.; Cheng, Z.; Xing, B. Photoactivable bioluminescent probes for imaging luciferase activity. Chem. Commun. 2009, 27, 4028-4030. (66) Zang, C.; Wang, H.; Li, T.; Zhang, Y.; Li, J.; Shang, M.; Du, J.; Xi, Z.; Zhou, C. A light-responsive, self-immolative linker for controlled drug delivery via peptide- and protein-drug conjugates. Chem. Sci. 2019, 10(39), 8973-8980. (67) Gill, K.; Mei, X.; Gillies, E. R. Self-immolative dendron hydrogels. Chem. Commun. 2021, 57(84), 11072-11075. (68) Hunter, F. W.; Wouters, B. G.; Wilson, W. R. Hypoxia-activated prodrugs: paths forward in the era of personalised medicine. Br. J. Cancer 2016, 114(10), 1071-1077. (69) Wang, Y.; Gray, J. P.; Mishin, V.; Heck, D. E.; Laskin, D. L.; Laskin, J. D. Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radic. Biol. Med. 2008, 44(6), 1169-1179. (70) Phillips, R. M. Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs. Cancer Chemother. Pharmacol. 2016, 77(3), 441-457. (71) Luo, S.; Zou, R.; Wu, J.; Landry, M. P. A probe for the detection of hypoxic cancer cells. ACS Sens. 2017, 2(8), 1139-1145. (72) Peng, X.; Gao, J.; Yuan, Y.; Liu, H.; Lei, W.; Li, S.; Zhang, J.; Wang, S. Hypoxia-activated and indomethacin-mediated theranostic prodrug releasing drug on-demand for tumor imaging and therapy. Bioconjugate Chem. 2019, 30(11), 2828-2843. (73) Szakonyi, Z.; Martinek, T. A.; Sillanpää, R.; Fülöp, F. Regio- and stereoselective synthesis of the enantiomers of monoterpene-based β-amino acid derivatives. Tetrahedron: Asymmetry 2007, 18(20), 2442-2447. (74) Chatterjee, S.; Bandyopadhyay, A. Cysteine-selective installation of functionally diverse boronic acid probes on peptides. Org. Lett. 2023, 25(13), 2223-2227. (75) Antermite, D.; Friis, S. D.; Johansson, J. R.; Putra, O. D.; Ackermann, L.; Johansson, M. J. Late-stage synthesis of heterobifunctional molecules for PROTAC applications via ruthenium-catalysed C‒H amidation. Nat. Commun. 2023, 14(1), 8222. (76) Mc Murry, J. E.; Scott, W. J. A method for the regiospecific synthesis of enol triflates by enolate trapping. Tetrahedron Lett. 1983, 24(10), 979-982. (77) Crisp, G. T.; Scott, W. J.; Stille, J. K. Palladium-catalyzed carbonylative coupling of vinyl triflates with organostannanes. A total synthesis of (.+-.)-. DELTA. 9 (12)-capnellene. J. Am. Chem. Soc. 1984, 106(24), 7500-7506. (78) Wulff, W. D.; Peterson, G. A.; Bauta, W. E.; Chan, K. S.; Faron, K. L.; Gilbertson, S. R.; Murray, C. K. A regioselective entry to vinyl lithiums from unsymmetrical ketones via enol triflates. J. Org. Chem. 1986, 51(2), 277-279. (79) Achilli, C.; Ciana, A.; Fagnoni, M.; Balduini, C.; Minetti, G. Susceptibility to hydrolysis of phenylboronic pinacol esters at physiological pH. Open Chem. 2013, 11(2), 137-139. (80) Michael, N. P.; Brehm, J. K.; Anlezark, G. M.; Minton, N. P. Physical characterisation of the Escherichia coli B gene encoding nitroreductase and its over-expression in Escherichia coli K12. FEMS Microbiol. Lett. 1994, 124(2), 195-202. (81) Anlezark, G. M.; Melton, R. G.; Sherwood, R. F.; Coles, B.; Friedlos, F.; Knox, R. J. The bioactivation of 5-(aziridin-1-yl)-2, 4-dinitrobenzamide (CB1954)—I: purification and properties of a nitroreductase enzyme from Escherichia coli—a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT). Biochem. Pharmacol. 1992, 44(12), 2289-2295. (82) Tang, J.; Ma, D.; Pecic, S.; Huang, C.; Zheng, J.; Li, J.; Yang, R. Noninvasive and highly selective monitoring of intracellular glucose via a two-step recognition-based nanokit. Anal. Chem. 2017, 89(16), 8319-8327. (83) Li, T.; Gu, Q. S.; Chao, J. J.; Liu, T.; Mao, G. J.; Li, Y.; Li, C. Y. An intestinal-targeting near-infrared probe for imaging nitroreductase in inflammatory bowel disease. Sens. Actuators B: Chem. 2024, 403, 135181. (84) Sebestyen, A.; Kopper, L.; Danko, T.; Timar, J. Hypoxia signaling in cancer: from basics to clinical practice. Pathol. Oncol. Res. 2021, 27, 1609802. (85) Lee, H. M.; Lee, S. C.; He, L.; Kong, A. P. S.; Mao, D.; Hou, Y.; Chan, J. C. N. Legacy effect of high glucose on promoting survival of HCT116 colorectal cancer cells by reducing endoplasmic reticulum stress response. Am. J. Cancer Res. 2021, 11(12), 6004. (86) Hsu, J. F.; Hsieh, P. Y.; Hsu, H. Y.; Shigeto, S. When cells divide: Label-free multimodal spectral imaging for exploratory molecular investigation of living cells during cytokinesis. Sci. Rep. 2015, 5, 17541. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/96618 | - |
| dc.description.abstract | 近年來，硼酸在化學生物學中的應用備受關注，並在治療研究、生物探針以及多種化學-生物研究領域取得了顯著的實際進展。然而，硼酸與其他親核試劑會產生非特異性結合，而硼酸酯在生物系統中的固有不穩定性限制了其在體內的應用。
在此我們利用δ-蒎烯雙醇衍生物開發了一種可控的硼酸籠策略，使硼酸能夠在特定刺激下釋放。δ-蒎烯雙醇做為保護基骨架，並引入含有鄰硝基或對硝基的芐基取代基作為觸發單元，這些觸發單元在UV照射或暴露於硝基還原酶後，會形成裸露的酚基或苯胺基團，透過自崩解反應，降低硼酸酯的穩定性，進而釋放出硼酸分子。我們利用這種具有刺激響應性的δ-蒎烯雙醇衍生物與雙硼酸類型的葡萄糖螢光探針結合，藉由可控釋放策略進行細胞內葡萄糖檢測，建立了一個具有優良時空選擇性的光響應硼酸酯探針。另外，我們的缺氧響應籠閉策略使葡萄糖探針能夠選擇性地靶向過度表達硝基還原酶的腫瘤細胞，幫助我們在混合的細胞中分辨癌細胞以及正常細胞。我們期待未來，刺激響應籠閉策略能夠在多種生物環境中可控釋放硼酸，拓展硼酸化學在生物體中的應用性。 | zh_TW |
| dc.description.abstract | In recent years, there has been a growing focus on the application of boronic acids in chemical biology, with significant practical progress made in areas such as therapeutic research, biological probes, and numerous chemical–biological studies. However, boronic acids exhibit nonspecific binding with other nucleophiles, and the inherent lability of boronic esters in biological systems limits their applications in vivo.
In this study, we have developed a controllable caging strategy for boronic acids using δ-pinanediol derivatives, enabling the release of boronic acids toward specific stimuli. Trigger units containing o-nitroaryl or p-nitroaryl groups were introduced onto δ-pinanediol. Upon UV irradiation or exposure to nitroreductase, these trigger units form a free phenol or aniline group, acting as self-immolative linkers, which destabilize the boronic ester, thereby releasing boronic acid molecules. Furthermore, we utilized our stimuli-responsive pinanediol cages in combination with a diboronic acid-based fluorescent glucose sensor. Through our controllable release strategies, intracellular glucose detection was conducted with a photoresponsive boronic ester probe with excellent spatiotemporal selectivity. Additionally, our hypoxia-responsive caging strategy has allowed glucose probes to selectively target tumor cells overexpressing nitroreductase, assisting us in distinguishing cancer cells from normal cells in co-cultured cell samples. In the future, stimuli-responsive caging strategies show promising potential for the controllable release of boronic acids in various biological contexts. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-02-20T16:13:46Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-02-20T16:13:46Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 i
中文摘要 ii Abstract iii Contents v List of Figures x List of Schemes xvi Abbreviation Table xvii Chapter 1 Introduction 1 1.1 Introduction of boronic acids in biological applications 1 1.2 Boronic acids as therapeutic reagents 3 1.3 Boronic acids as bioorthogonal probes 5 1.4 Boronic acids as saccharide sensors 8 1.5 Boronic acid as caged bioactive compounds or nanocarriers 11 1.6 Stability of boronic esters 14 1.7 Self-immolative chemistry- o-nitrobenzyl group as a photo trigger unit in biological systems 17 1.8 Self-immolative chemistry- p-nitrobenzyl group as hypoxia trigger unit in biological systems 20 Chapter 2 Results and discussion 25 2.1 Molecular design 25 2.2 Design and characteristics of the diol scaffolds. 29 2.2.1 Synthesis of the diol scaffolds tPin-EtPh (2) and kPin-EtPh (7) 29 2.2.2 Hydrolytic stability evaluation with the diol scaffolds 30 2.3 Design and characteristics studies of the pinanediol cages 33 2.3.1 Synthesis of the photoresponsive pinanediol cage oNB-kPin-diol (16) 33 2.3.2 Synthesis of the hypoxia-responsive pinanediol cage pNB-kPin-diol (28) 36 2.3.3 Synthesis of the hypoxia-responsive pinanediol cage NP-kPin-diol (24) 37 2.3.4 Synthesis of the pinanediol cage Ph-kPin-diol (21) 37 2.3.5 Hydrolytic stability evaluation with the pinanediol cages 38 2.3.6 Stimuli-responsiveness of pinanediol cages with trigger units 40 2.3.7 Hydrolytic stability evaluation with the pinanediol cages with or without stimulus 45 2.3.8 Pinanediol-caged boronic esters show high tolerance to environmental pH 46 2.4 Mechanistic study of the release strategies of pinanediol-caged boronic acids 49 2.5 Employment of our controlling strategies for glucose-sensitive boronic acid-based sensors. 53 2.5.1 Synthesis of McCDBA 54 2.5.2 Demonstration of stimuli-responsive pinanediol cages for the glucose sensor McCDBA in physiological conditions. 55 2.5.3 Evaluation of the pH dependency of McCDBA with the four pinanediol cages 58 2.6 Our photoresponsive strategy provides glucose detection with spatiotemporal selectivity. 61 2.6.1 Evaluation of uptake efficiency of McCDBA by HeLa cells. 61 2.6.2 Cytotoxicity assays towards HeLa cells 62 2.6.3 Demonstration of controllable cellular glucose detection by the photoresponsive pinanediol cage with McCDBA. 63 2.6.4 Direct photoactivation of cellular-caged McCDBA 65 2.7 Our hypoxia-responsive strategies assist glucose sensors in the selective labeling of cancer cells.. 68 2.7.1 Cytotoxicity assays towards HEK293T and HCT 116 cells 68 2.7.2 Demonstration of cancer cell-selective labeling by the hypoxia-responsive pinanediol cage with McCDBA. 69 2.7.3 Demonstration of cancer cell-selective labeling by hypoxia-responsive pinanediol cages with McCDBA. 74 2.7.4 Demonstration of cancer cell-selective labeling with cocultured cells samples. 77 Chapter 3 Conclusion 80 Chapter 4 Methods 83 4.1. General methods and instruments 83 4.2. Synthesis and characterization of compounds 85 4.3. Hydrolysis, assembly and fluorescence detection assays 113 4.3.1 General methods 113 4.3.2 Hydrolysis and assembly assays 114 4.3.3 Fluorescence detection with McCDBA and pinanediol cages 115 4.4. Determination of the binding constants 116 4.4.1 Determination of the binding constants (Ka) between D-glucose and McCDBA 116 4.4.2 Determination of the apparent binding constants (Kapp) between pinanediol cages and McCDBA 117 4.5. Cell experiments 120 4.5.1 Cell line and cell culture 120 4.5.2 Cytotoxicity assays 121 4.5.3 Cell uptake assays 121 4.5.4 Method for fluorescent imaging of cells with the photoresponsive pinanediol cage 122 4.5.5 Method for fluorescent imaging of cells with regioselective irradiation 123 4.5.6 Method for fluorescent imaging of normal and tumor cells with the hypoxia-responsive pinanediol cages 124 References 125 Appendix I: Mass spectra of boronic esters and pinanediol cages 136 Appendix II: HPLC of the assembly of PhEtBA and pinanediol cages 139 Appendix III: NMR Spectroscopic Data 141 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 硼酯 | zh_TW |
| dc.subject | 籠閉策略 | zh_TW |
| dc.subject | 自崩解 | zh_TW |
| dc.subject | 刺激響應 | zh_TW |
| dc.subject | 蒎烯雙醇 | zh_TW |
| dc.subject | 硼酸 | zh_TW |
| dc.subject | stimuli-responsive | en |
| dc.subject | pinanediol | en |
| dc.subject | boronic esters | en |
| dc.subject | boronic acids | en |
| dc.subject | caging strategy | en |
| dc.subject | self-immolative | en |
| dc.title | 適用於生物系統中的多功能刺激響應型蒎烯雙醇籠閉分子對硼酸的動態組裝和釋放策略 | zh_TW |
| dc.title | Versatile stimuli-responsive pinanediol cages for boronic acids in biological systems: Dynamic assembly and release | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-1 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 方俊民;李賢明;謝俊結;朱忠瀚 | zh_TW |
| dc.contributor.oralexamcommittee | Jim-Min Fang;Hsien-Ming Lee;Jiun-Jie Shie;Chung-Han Chu | en |
| dc.subject.keyword | 硼酸,硼酯,蒎烯雙醇,刺激響應,自崩解,籠閉策略, | zh_TW |
| dc.subject.keyword | boronic acids,boronic esters,pinanediol,stimuli-responsive,self-immolative,caging strategy, | en |
| dc.relation.page | 166 | - |
| dc.identifier.doi | 10.6342/NTU202500226 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-01-21 | - |
| dc.contributor.author-college | 理學院 | - |
| dc.contributor.author-dept | 化學系 | - |
| dc.date.embargo-lift | 2030-01-20 | - |
| 顯示於系所單位： | 化學系 | |
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