TY - JOUR
T1 - Development of a Series of Practical Fluorescent Chemical Tools to Measure pH Values in Living Samples
AU - Takahashi, Shodai
AU - Kagami, Yu
AU - Hanaoka, Kenjiro
AU - Terai, Takuya
AU - Komatsu, Toru
AU - Ueno, Tasuku
AU - Uchiyama, Masanobu
AU - Koyama-Honda, Ikuko
AU - Mizushima, Noboru
AU - Taguchi, Tomohiko
AU - Arai, Hiroyuki
AU - Nagano, Tetsuo
AU - Urano, Yasuteru
N1 - Funding Information:
This work was supported in part by grants by JSPS KAKENHI Grant Numbers 16H00823 and 16H05099 to K.H., 16H06574 to T.U. and KAKENHI (S) (No. 17H06173) (to M.U.) and SENTAN, JST to K.H., who was also supported by a grant JSPS Core-to-Core program, A. Advanced Research Networks, and Mochida Memorial Foundation for Medical and Pharmaceutical Research.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/5/9
Y1 - 2018/5/9
N2 - In biological systems, the pH in intracellular organelles or tissues is strictly regulated, and differences of pH are deeply related to key biological events such as protein degradation, intracellular trafficking, renal failure, and cancer. Ratiometric fluorescence imaging is useful for determination of precise pH values, but existing fluorescence probes have substantial limitations, such as inappropriate pKa for imaging in the physiological pH range, inadequate photobleaching resistance, and insufficiently long excitation and emission wavelengths. Here we report a versatile scaffold for ratiometric fluorescence pH probes, based on asymmetric rhodamine. To demonstrate its usefulness for biological applications, we employed it to develop two probes. (1) SiRpH5 has suitable pKa and water solubility for imaging in acidic intracellular compartments; by using transferrin tagged with SiRpH5, we achieved time-lapse imaging of pH in endocytic compartments during protein trafficking for the first time. (2) Me-pEPPR is a near-infrared (NIR) probe; by using dextrin tagged with Me-pEPPR, we were able to image extracellular pH of renal tubules and tumors in situ. These chemical tools should be useful for studying the influence of intra- and extracellular pH on biological processes, as well as for in vivo imaging.
AB - In biological systems, the pH in intracellular organelles or tissues is strictly regulated, and differences of pH are deeply related to key biological events such as protein degradation, intracellular trafficking, renal failure, and cancer. Ratiometric fluorescence imaging is useful for determination of precise pH values, but existing fluorescence probes have substantial limitations, such as inappropriate pKa for imaging in the physiological pH range, inadequate photobleaching resistance, and insufficiently long excitation and emission wavelengths. Here we report a versatile scaffold for ratiometric fluorescence pH probes, based on asymmetric rhodamine. To demonstrate its usefulness for biological applications, we employed it to develop two probes. (1) SiRpH5 has suitable pKa and water solubility for imaging in acidic intracellular compartments; by using transferrin tagged with SiRpH5, we achieved time-lapse imaging of pH in endocytic compartments during protein trafficking for the first time. (2) Me-pEPPR is a near-infrared (NIR) probe; by using dextrin tagged with Me-pEPPR, we were able to image extracellular pH of renal tubules and tumors in situ. These chemical tools should be useful for studying the influence of intra- and extracellular pH on biological processes, as well as for in vivo imaging.
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U2 - 10.1021/jacs.8b00277
DO - 10.1021/jacs.8b00277
M3 - Article
C2 - 29688713
AN - SCOPUS:85046888949
SN - 0002-7863
VL - 140
SP - 5925
EP - 5933
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 18
ER -
