陳錦地老師實驗室設計出具有推、拉電子結構的螢光團，且不共平面的共軛結構使螢光團具有誘導堆疊放光的特性，並以帶正電荷或負電荷離子修飾增加親水性，開發此系列螢光團對生物相關及醫學研究應用性。
將此系列螢光團修飾在胜肽上，作為偵測蛋白激酶A活性的生物探針，蛋白激酶A在細胞內能催化蛋白質磷酸化，參與細胞內代謝、凋亡、分化…等重要生理機能，蛋白激酶A功能異常與癌症或神經衰退重要疾病有高度相關性。
本實驗利用鑭系元素氧化物吸附磷酸化胜肽，且氧化物不溶於水可誘導螢光團堆疊放光，搭配濾紙過濾固體並利用以螢光強度作為磷酸化胜肽半定量，胜肽磷酸化程度取決於蛋白激酶A活性強弱，成功開發具有專一性蛋白激酶活性螢光快篩方法。

We synthesized a series of aggregation-induced emission (AIE) dyes which were designed by Dr. Chin-Ti Chen’s group. The AIE dyes have nonplanar conjugat-ed structure which is crucial to provide the unique fluorescent turn-on property upon aggregation. In order to increase water solubility of our probes, we modified AIE dyes with hydrophilic ligands such as positively charge ammonium group or nega-tively charged sulfite group.
Kinase family is responsible for catalyzing intracellular protein phosphoryla-tion. It is one of the most important enzymes target in human diseases including cancer and neurodegenerative disorders. To apply AIE dyes in detection of biological events, we coupled AIE dye with peptide substrate as bioluminescent probe for Pro-tein Kinase A (PKA) detection.
We used lanthanum(III) oxide that can interact with phosphorylated AIE-peptide, and its poor solubility in water enhanced the AIE fluorescence. The solid mixture was then immobilized on a filter paper for quantitative analysis of PKA activity. The approach is potentially useful as a rapid kinase activity detection kit based on AIE dyes.

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2. Wang, H.; Zhao, E. G.; Lam, J. W. Y.; Tang, B. Z., AIE luminogens: emission brightened by aggregation. Materials Today 2015, 18 (7), 365-377.
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1. Luo, J. D.; Xie, Z. L.; Lam, J. W. Y.; Cheng, L.; Chen, H. Y.; Qiu, C. F.; Kwok, H. S.; Zhan, X. W.; Liu, Y. Q.; Zhu, D. B.; Tang, B. Z., Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. Chemical Communications 2001, (18), 1740-1741.
2. Wang, H.; Zhao, E. G.; Lam, J. W. Y.; Tang, B. Z., AIE luminogens: emission brightened by aggregation. Materials Today 2015, 18 (7), 365-377.
3. Bhongale, C. J.; Chang, C. W.; Lee, C. S.; Diau, E. W. G.; Hsu, C. S., Relaxation dynamics and structural characterization of organic nanoparticles with enhanced emission. Journal of Physical Chemistry B 2005, 109 (28), 13472-13482.
4. Hong, Y. N.; Lam, J. W. Y.; Tang, B. Z., Aggregation-induced emission. Chemical Society Reviews 2011, 40 (11), 5361-5388.
5. Wu, J. S.; Liu, W. M.; Ge, J. C.; Zhang, H. Y.; Wang, P. F., New sensing mechanisms for design of fluorescent chemosensors emerging in recent years. Chemical Society Reviews 2011, 40 (7), 3483-3495.
6. Kwok, R. T. K.; Leung, C. W. T.; Lam, J. W. Y.; Tang, B. Z., Biosensing by luminogens with aggregation-induced emission characteristics. Chemical Society Reviews 2015, 44 (13), 4228-4238.
7. Liu, H. L.; Song, P. S.; Wei, R. R.; Li, K.; Tong, A. J., A facile, sensitive and selective fluorescent probe for heparin based on aggregation-induced emission. Talanta 2014, 118, 348-352.
8. Shi, H. B.; Kwok, R. T. K.; Liu, J. Z.; Xing, B. G.; Tang, B. Z.; Liu, B., Real-Time Monitoring of Cell Apoptosis and Drug Screening Using Fluorescent Light-Up Probe with Aggregation-Induced Emission Characteristics. Journal of the American Chemical Society 2012, 134 (43), 17972-17981.
9. Arrington, J. V.; Hsu, C. C.; Elder, S. G.; Tao, W. A., Recent advances in phosphoproteomics and application to neurological diseases. Analyst 2017, 142 (23), 4373-4387.
10. Paradela, A.; Pablo Albar, J., Advances in the analysis of protein phosphorylation. Journal of Proteome Research 2008, 7 (5), 1809-1818.
11. Machida, M.; Kosako, H.; Shirakabe, K.; Kobayashi, M.; Ushiyama, M.; Inagawa, J.; Hirano, J.; Nakano, T.; Bando, Y.; Nishida, E.; Hattori, S., Purification of phosphoproteins by immobilized metal affinity chromatography and its application to phosphoproteome analysis. Febs Journal 2007, 274 (6), 1576-1587.
12. Nelson, C. A.; Szczech, J. R.; Xu, Q. G.; Lawrence, M. J.; Jin, S.; Ge, Y., Mesoporous zirconium oxide nanomaterials effectively enrich phosphopeptides for mass spectrometry-based phosphoproteomics. Chemical Communications 2009, (43), 6607-6609.
13. Leitner, A., Phosphopeptide enrichment using metal oxide affinity chromatography. Trac-Trends in Analytical Chemistry 2010, 29 (2), 177-185.
14. Lin, B.; Li, T.; Zhao, Y.; Huang, F.-K.; Guo, L.; Feng, Y.-Q., Preparation of a TiO2 nanoparticle-deposited capillary column by liquid phase deposition and its application in phosphopeptide analysis. Journal of Chromatography A 2008, 1192 (1), 95-102.
15. Jabeen, F.; Najam-ul-Haq, M.; Ashiq, M. N.; Rainer, M.; Huck, C. W.; Bonn, G. K., Gadolinium oxide: Exclusive selectivity and sensitivity in the enrichment of phosphorylated biomolecules. Journal of Separation Science 2016, 39 (21), 4175-4182.
16. Zhou, J.; Du, X. W.; Berciu, C.; He, H. J.; Shi, J. F.; Nicastro, D.; Xu, B., Enzyme-Instructed Self-Assembly for Spatiotemporal Profiling of the Activities of Alkaline Phosphatases on Live Cells. Chem 2016, 1 (2).
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18. Hu, R. R.; Lager, E.; Aguilar-Aguilar, A.; Liu, J. Z.; Lam, J. W. Y.; Sung, H. H. Y.; Williams, I. D.; Zhong, Y. C.; Wong, K. S.; Pena-Cabrera, E.; Tang, B. Z., Twisted Intramolecular Charge Transfer and Aggregation-Induced Emission of BODIPY Derivatives. Journal of Physical Chemistry C 2009, 113 (36), 15845-15853.
19. Lei, C.; Zhou, L.; Xu, C.; Sun, X. R.; Nouwens, A.; Yu, C. Z., Binder-Free TiO2 Monolith-Packed Pipette Tips for the Enrichment of Phosphorylated Peptides. Australian Journal of Chemistry 2016, 69 (12), 1396-1401.
20. Fukuda, I.; Hirabayashi-Ishioka, Y.; Sakikawa, I.; Ota, T.; Yokoyama, M.; Uchiumi, T.; Morita, A., Optimization of Enrichment Conditions on TiO2 Chromatography Using Glycerol As an Additive Reagent for Effective Phosphoproteomic Analysis. Journal of Proteome Research 2013, 12 (12), 5587-5597.
21. Yoo, H. J.; Hakansson, K., Phosphate-containing Metabolite Enrichment with TiO2 Micro-tips. Bulletin of the Korean Chemical Society 2012, 33 (8), 2475-2476.
22. Irague, R., Topham, C. M., Martineau, N., Baylac, A., Auriol, C., Walther, T., Francois, J. M., Andre, I. and Remaud-Simeon, M., A generic HTS assay for kinase screening: Validation for the isolation of an engineered malate kinase, Plos One 2018, 13 (2), 1-15.