研究领域
Chemical Biology & Bioimaging
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)]
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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
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
The small molecule probe PT-Yellow labels the renal proximal tubules in zebrafish, Sander, V.; Patke, S. V.; Sahu, S.; Teoh, C. L.; Peng, P.; Chang, Y. T.; Davidson, A. J. Chem. Commun. 2015, 51, 395-398
Sensitive multiplex detection of serological liver cancer biomarkers using SERS active photonic crystal fiber probe, Dinish, U. S; Balasundaram, G.; Chang, Y. T.; Olivo, M. J. Biophotonics 2014, 7, 956-965
Dark to light! A new strategy for large Stokes shift dyes: coupling of a dark donor with tunable high quantum yield acceptors, Su, D. D.; Oh, J.; Lee, S. C.; Lim, J. M.; Sahu, S.; Yu, X.; Kim, D.*; Chang, Y. T.* Chem. Sci. 2014, 5, 4812-4818
Chemical targeting of GAPDH moonlighting function in cancer cells reveals its role in tubulin regulation, Jung, D. W.; Kim, W. H.; Seo, S.; Oh, E.; Yim, S. H.; Ha, H. H.; Chang, Y. T.; Williams, D. R. Chem. Biol. 2014, 21, 1533-1545
Investigating fluorescent dyes in fluorescence-assisted screening, Jee, J. E.; Lim, J.; Hyun, H.; Oon, J.; Ong, Y. S.; Massif, C.; Chang, Y. T.; Choi, H. S.; Lee, S. S. Chem. Commun. 2014, 50, 15220-15223
A molecular fluorescent probe for targeted visualization of temperature at the endoplasmic reticulum, Arai, S.; Lee, S. C.; Zhai, D.; Suzuki, M.; Chang, Y. T.* Sci. Rep. 2014, 4, 6701
CDr10b inhibits the expression of cyclooxygenase-2 and inducible nitric oxide synthase induced by lipopolysaccharide, Gu, G. J.; Lim, S. J.; Ahn, S. I.; Lee, S. C.; Chang, Y. T.; Choi, T. H.; Kim, B. S.; Eom, Y. B.; Lee, N. K.; Youn, H. S. Eur. J. Pharmacol. 2014, 742, 42-46
In Situ Investigation of Mammalian Inorganic Polyphosphate Localization Using Novel Selective Fluorescent Probes JC-D7 and JC-D8, Angelova, P. R.; Agrawalla, B. K.; Elustondo, P. A.; Gordon, J.; Shiba, T.; Abramov, A. Y.; Chang, Y. T.*; Pavlov, E. V.* ACS Chem Biol. 2014, 9, 2101-2110
An artificial tongue fluorescent sensor array for identification and quantitation of various heavy metal ions, Xu, W.; Ren, C.; Teoh, C. L.; Peng, J.; Gadre, S. H.; Rhee, H. W.*; Lee, C. L. K.*; Chang, Y. T.* Anal. Chem. 2014, 86, 8763-8769
Inhibition of tau aggregation by a rosamine derivative that blocks tau intermolecular disulfide cross-linking, Haque, M. M.; Kim, D.; Yu, Y. H.; Lim, S.; Kim, D. J.; Chang, Y. T.; Ha, H. H.; Kim, Y. K. Amyloid 2014, 21, 185-190
Milk quality control: instant and quantitative milk fat determination with a BODIPY sensor-based fluorescence detector, Xu, W.; Bai, J.; Peng, J.; Samanta, A.; Divyanshu; Chang, Y. T.* Chem. Commun. 2014, 50, 10398-10410
In vivo detection of macrophage recruitment in hind-limb ischemia using a targeted near-infrared fluorophore, Yoo, J. S.; Das, R. K.; Jow, Z. Y.; Chang, Y. T.* Plos One 2014, 9, e103721
A fluorescent probe for imaging symmetric and asymmetric cell division in neurospher formation, Yun, S. W.; Leong, C.; Bi, X.; Ha, H. H.; Yu, Y. H.; Tan, Y. L.; Narayanan, G.; Sankaran, S.; Kim, J. Y.; Hariharan, S.; Ahmed, S.*; Chang, Y. T.* Chem. Commun. 2014, 50, 7492-7494
A macrophage uptaking near-infrared chemical probe for in vivo imaging of inflammation, Kang, N. Y.; Park, S. J.; Ang, X. W.; Samanta, A.; Driessen, W. H.; Ntziachristos, V.; Vasquez, K. O.; Peterson, J. D.; Yun, S. W.*; Chang, Y. T.* Chem. Commun. 2014, 50, 6589-6591
Live cells imaging using a turn-on FRET-based BODIPY probe for biothiols, Su, D.; Teoh, C. L.; Sahu, S.; Das, R. K.; Chang, Y. T.* Biomaterials 2014, 35, 6078-6085
Biocompatible surface-enhanced Raman Scattering nanotags for in vivo cancer detection, Samanta, A.; Jana, S.; Chang, Y. T.* Nanomedicine 2014, 9, 523-535
Multiplexing SERS nanotags for the imaging of differentiated mouse embryonic stem cells (mESC) and detection of teratoma in vivo, Samanta, A.; Das, R. K.; Park, S. J.; Maiti, K. K.; Chang, Y. T.* Am. J. Nucl. Med. Mol. Imaging 2014, 4, 114-124
A Chemical Probe Selective for Human Pluripotent Stem Cells, Hirata, N.; Nakagawa, M.; Fujibayashi, Y.; Yamauchi, K.; Murata, A.; Minami, I.; Tomioka, M.; Kondo, T.; Kuo, T. F.; Endo, H.; Inoue, H.; Sato, S. I.; Ando, S.; Kawazoe, Y.; Aiba, K.; Nagata, K.; Kawase, E.; Chang, Y. T.; Suemori, H.; Eto, K.; Nakauchi, H.; Yamanaka, S.; Nakatsuji, N.; Ueda, K.; Uesugi1, M. Cell Rep. 2014, 6, 1165-1174