Professor CHANG Young-Tae

Post-doc., Univ. of California at Berkeley/Scripps Research Inst., 1997-2000; Ph.D., POSTECH, 1996; M.Sc., POSTECH, 1994; B.Sc., POSTECH, 1991

Contact Information

Department of Chemistry, NUS
3 Science Drive 3
Singapore 117543
Office: MD1-17-03C
Tel: (65) 6516-6774
Fax: (65)-6779-1691
Email: chmcyt@nus.edu.sg


Research Interests

 

Diversity-oriented fluorescence library approach (DOFLA) for sensors/probes development

Fluorescent dyes have been widely used as sensors and probes due to their high sensitivity and exceptional ease of handling. The conventional “analyte oriented approach”, which modify the dye molecule according to the known recognition motif, has succeeded to improve the target specificity, however it limited the scope and speed of novel sensor discovery. Based on this conventional method, many useful probes have been discovered but essentially by accidents. Our group introduced a new “diversity oriented approach” using fluorescent dye library, in other words diversity oriented fluorescence library. Our ability to discover new sensors was improved dramatically by the combination of two new technologies, combinatorial chemistry and high-throughput screening. Thousands of structurally diverse fluorescence molecules were synthesized by a combinatorial synthesis technique, and high-throughput screening methodology employed to evaluate a large number of dyes automatically to discover fluorescence sensors for many different kinds of targets. Surprisingly, specific and unique sensors for a broad range of analytes from macromolecules including DNA, RNA and proteins, to various small molecules could be discovered from DOFL, demonstrating the universal applicability of this approach. We are currently testing DOFL compounds for various stem cells (Figure 1) and pancreatic alpha & beta cells for in vitro and in vivo imaging.

Figure 1. Stem Cell selective probe development by DOFLA

Artificial Tongue

As a mimic of mammalian tongue, researchers developed the concept of sensors array comprised of various dyes which can show unique patterns to different analytes. To maximize the discrimination power, our group investigated many commercial dyes and our own DOFL compounds. The most-sensitive and chemically stable dyes were selected based on their stability, solubility, and color change kinetics (fast and stable color change), and dubbed “Artificial Tongue(New York Tongue: NYT, Singapore Tongue: SGT)”. Similar to human tongue, our artificial tongue system was designed to be a universal sensor. We published several interesting results of the discrimination of diverse analyte sets including metal cations, carbohydrates, and even tap waters (Figure 2) using this concept.

Figure 2 Colorimetric sensor array for cation discrimination. 47 off-the-shelf dyes were configured as a colorimetric sensor array (left: digital camera image of NYT-1 with/without analyte), and color change pattern was analyzed by multivariable classification method (center: heatmap and hierarchical clustering, right: principal component analysis)]

Representative Publications

  • Development of background-free tame fluorescent probes for intracellular live cell imaging, Alamudi, S. H.; Satapathy, R.; Kim, J.; Su, D.; Ren, H.; Das, R.; Hu, L.; Alvarado-Martínez, E.; Lee, J. Y.; Hoppmann, C.; Peña-Cabrera, E.; Ha, H. H.; Park, H. S.; Wang, L.; Chang, Y. T. Nat. Commun. 2016, 7, doi: 10.1038/ncomms11964.

  • Boronic acid: a bio-inspired strategy to increase the sensitivity and selectivity of fluorescent NADH probe, Wang, L; Zhang, J.; Kim, B.; Peng, J.; Berry, S. N.; Ni, Y.; Su, D.; Lee, J.; Yuan, L.; Chang, Y. T. J. Am. Chem. Soc. 2016, 138, 10394-10397.

  • Development of a highly selective, sensitive and fast response upconversion luminescent platform for hydrogen sulfide detection, Peng, J.; Teoh, C. L.; Zeng, X.; Samanta, A.; Wang, L.; Xu, W.;  Su, D.; Yuan, L., Liu, X.; Chang, Y. T. Adv. Funct. Mat. 2016, 26, 191-199.

  • Detection of pathogenic biofilms with bacterial amyloid targeting fluorescent probe, CDy11, Kim, J. Y.; Sahu, S.; Yau, Y. H.; Wang, X.; Shochat, S. G.; Nielsen, P. H.; Dueholm, M. S.; Otzen, D. E.; Lee, J.; Delos Santos, M. M.; Yam, J. K.; Kang, N. Y.; Park, S. J.; Kwon, H.; Seviour, T. W.; Yang, L.; Givskov, M.; Chang, Y. T. J. Am. Chem. Soc. 2016, 138, 402-407.

  • Multisite-binding switchable fluorescent probe for monitoring mitochondrial ATP level fluctuation in live cells, Wang, L.; Yuan, L.; Zeng, X.; Peng, J.; Ni, Y.; Er, J. C.; Xu, W. Agrawalla, B. K.; Su, D.; Kim, B.; Chang, Y. T. Angew. Chem., Int. Ed. Engl. 2016, 55, 1773-1776.

  • Chemical Fluorescent Probe for Detection of Aβ Oligomers, Teoh, C. L.; Su, D.; Sahu, S.; Yun, S. W.; Drummond, E.; Prelli, F.; Lim, S.; Cho, S.; Ham, S.; Wisniewski, T.; Chang, Y. T. J. Am. Chem. Soc. 2015, 137, 13503-13509. Spotlights on Recent JACS Publications at J. Am . Chem. Soc. 2015, 137, 10017. (http://pubs.acs.org/doi/pdf/10.1021/jacs.5b08475)

  • Development of Targetable Two-Photon Fluorescent Probes to Image Hypochlorous Acid in Mitochondria and Lysosome in Live Cell and Inflamed Mouse Model, Yuan, L.; Wang, L.; Agrawalla, B. K.; Park, S. J.; Zhu, H.; Sivaraman, B.; Peng, J.; Xu, Q. H.; Chang, Y. T. J. Am. Chem. Soc. 2015, 137, 5930-5938.

  • Glucagon-secreting alpha cell selective two-photon fluorescent probe TP-α: for live pancreatic islet imaging, Agrawalla, B. K.; Chandran, Y.; Phue, W. H.; Lee, S. C.; Jeong, Y. M.; Wan, S. Y.; Kang, N. Y.; Chang, Y. T. J. Am. Chem. Soc. 2015, 137, 5355-5362.

  • NeuO: a fluorescent chemical probe for live neuron labeling, Er, J. C.; Leong, C.; Teoh, C. L.; Yuan, Q.; Merchant, P.; Dunn, M.; Sulzer, D.; Sames, D.; Bhinge, A.; Kim, D.; Kim, S. M.; Yoon, M. H.; Stanton, L. W.; Je, S. H.; Yun, S. W.; Chang, Y. T. Angew. Chem., Int. Ed. Engl. 2015, 54, 2442-2446. Highlighted at “A library of bright ideas, C&En News, 2015 (March 23), 93 (12), p 39-40”

  • High-efficiency in vitro and in vivo detection of Zn2+ by dye-assembled upconversion nanoparticles, Peng, J.; Xu, W.; Teoh, C. L.; Han, S.; Kim, B.; Samanta, A.; Er. J. C.; Wang, L.; Yuan, L.; Liu, X.; Chang, Y. T. J. Am. Chem. Soc. 2015, 137, 2336-2342.