Holding-Oriented versus Gating-Oriented Live-Cell Distinction: Highlighting the Role of Transporters in Cell Imaging Probe Development
- Yun-Kyu Choi
Yun-Kyu ChoiDepartment of Chemistry, Pohang University of Science and Technology, Pohang 37673, Republic of KoreaMore by Yun-Kyu Choi
- ,
- Jong-Jin Kim
Jong-Jin KimCenter for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 37673, Republic of KoreaMore by Jong-Jin Kim
- , and
- Young-Tae Chang*
Young-Tae Chang*E-mail: [email protected]Department of Chemistry, Pohang University of Science and Technology, Pohang 37673, Republic of KoreaCenter for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 37673, Republic of KoreaMore by Young-Tae Chang
Abstract
Conspectus
Small molecule imaging probes are powerful tools to understand complex biological systems. The mainstreams of imaging probe developments have been focused on the target holding of the probes; the holding targets are often cell-type-specific biomarkers. This type of the probe mechanism can be designated as holding-oriented live-cell distinction (HOLD).
Our group has worked on the development of cell-type-selective probes using a diversity-oriented fluorescence library approach (DOFLA), where unbiased phenotypic screening is employed using fluorescent library compounds. Through the conventional target identification methods such as an affinity-based analysis, we elucidated that some of the probe mechanisms are HOLD. However, we also realized that sometimes there is no specific holding target for probes or the holding targets are ubiquitous.
The observation led us to test an alternative mechanism of cell-type-specific probes as gating-oriented live-cell distinction (GOLD). We started to examine the gating mechanism of probes, which is mainly based on transporters but which does not necessarily require probe holding to cellular targets. Transporters can control the in and out movement of various nutrients and chemicals. Different expression levels of transporters in various cell types could provide the molecular mechanism of differential staining of cells by regulating the intracellular accumulation of a certain specific probe. A number of GOLD probes have been developed by modifying or mimicking endogenous substrates of transporters such as inorganic ions, glucose, amino acids, or neurotransmitters, utilizing broad substrate specificity of transporters. The radiolabeled or fluorophore-conjugated substrate mimetics have been widely used for live cell distinction and various applications such as disease-related cell or tissue imaging.
In humans, there are about 400 solute carrier (SLC) transporters and 50 ATP-binding cassette (ABC) transporters. Since some transporters have broad substrate specificity, they can transport not only derivatives of endogenous natural substrates but also totally synthetic diverse imaging probes, such as DOFLA probes. Without preconsidering the structure of endogenous substrates, we recently demonstrated a series of live-cell imaging probes and elucidated their molecular mechanism as a gating one, either by SLC or ABC transporters. Transporter inhibitor panel and CRISPR-based transporter libraries could provide a systematic gating target elucidation platform.
Considering the generality of DOFLA and the CRISPR-based genomic tool for transporter systems (>450 in humans), the GOLD approach will offer new insight and promise for unprecedented levels of novel cell imaging probe development.
Cited By
This article is cited by 19 publications.
- Haw-Young Kwon, Raj Kumar Das, Gun Tae Jung, Hong-Guen Lee, Sun Hyeok Lee, Stuart N. Berry, Justin Kok Soon Tan, Solip Park, Jae-Seong Yang, Soohyun Park, Kangkyun Baek, Kyeng Min Park, Jae Won Lee, Yun-Kyu Choi, Ki Hean Kim, Sangho Kim, Kwang Pyo Kim, Nam-Young Kang, Kimoon Kim, Young-Tae Chang. Lipid-Oriented Live-Cell Distinction of B and T Lymphocytes. Journal of the American Chemical Society 2021, 143 (15) , 5836-5844. https://doi.org/10.1021/jacs.1c00944
- Heewon Cho, Na-Kyeong Hong, Young-Tae Chang. Novel Fluorescent Strategy for Discriminating T and B Lymphocytes Using Transport System. Pharmaceutics 2024, 16 (3) , 424. https://doi.org/10.3390/pharmaceutics16030424
- Larissa Miasiro Ciaramicoli, Young‐Tae Chang. Chemical probes based on GOLD : The discovery and elucidation of mechanism. Bulletin of the Korean Chemical Society 2023, 44 (8) , 679-692. https://doi.org/10.1002/bkcs.12713
- Yangzhi Kong, Qunying Jiang, Fan Zhang, Yang Yang. Small Molecular Fluorescent Probes: Application Progress of Specific Bacteria Detection and Antibacterial Phototherapy. Chemistry – An Asian Journal 2023, 18 (11) https://doi.org/10.1002/asia.202300178
- Seong-Hyeon Park, Hong-Guen Lee, Xiao Liu, Sung Kwang Lee, Young-Tae Chang. Quantitative Structure-Activity Relationship of Fluorescent Probes and Their Intracellular Localizations. Chemosensors 2023, 11 (5) , 310. https://doi.org/10.3390/chemosensors11050310
- Animesh Samanta, Subrata Munan, Anal Jana, Young Tae Chang. Diversity-oriented Fluorescence Library Approach: Accelerating Probe Development for Biological and Environmental Applications. 2023, 67-105. https://doi.org/10.1039/9781839167324-00067
- Mian Wang, Hongle An, Wensheng Cai, Xueguang Shao. Wavelet Transform Makes Water an Outstanding Near-Infrared Spectroscopic Probe. Chemosensors 2023, 11 (1) , 37. https://doi.org/10.3390/chemosensors11010037
- Gangwei Jiang, Tian-Bing Ren, Elisa D’Este, Mengyi Xiong, Bin Xiong, Kai Johnsson, Xiao-Bing Zhang, Lu Wang, Lin Yuan. A synergistic strategy to develop photostable and bright dyes with long Stokes shift for nanoscopy. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-29547-3
- Heewon Cho, Haw-Young Kwon, Amit Sharma, Sun Hyeok Lee, Xiao Liu, Naoki Miyamoto, Jong-Jin Kim, Sin-Hyeog Im, Nam-Young Kang, Young-Tae Chang. Visualizing inflammation with an M1 macrophage selective probe via GLUT1 as the gating target. Nature Communications 2022, 13 (1) https://doi.org/10.1038/s41467-022-33526-z
- Min Gao, Sun Hyeok Lee, Raj Kumar Das, Haw‐Young Kwon, Heon Seok Kim, Young‐Tae Chang. A SLC35C2 Transporter‐Targeting Fluorescent Probe for the Selective Detection of B Lymphocytes Identified by SLC‐CRISPRi and Unbiased Fluorescence Library Screening. Angewandte Chemie 2022, 134 (36) https://doi.org/10.1002/ange.202202095
- Min Gao, Sun Hyeok Lee, Raj Kumar Das, Haw‐Young Kwon, Heon Seok Kim, Young‐Tae Chang. A SLC35C2 Transporter‐Targeting Fluorescent Probe for the Selective Detection of B Lymphocytes Identified by SLC‐CRISPRi and Unbiased Fluorescence Library Screening. Angewandte Chemie International Edition 2022, 61 (36) https://doi.org/10.1002/anie.202202095
- Keun-Tae Kim, Ji-Young Oh, Seokwoo Park, Seong-Min Kim, Patterson Benjamin, In-Hyun Park, Kwang-Hoon Chun, Young-Tae Chang, Hyuk-Jin Cha. Live isolation of naïve ESCs via distinct glucose metabolism and stored glycogen. Metabolic Engineering 2022, 72 , 97-106. https://doi.org/10.1016/j.ymben.2022.03.003
- Larissa Miasiro Ciaramicoli, Heon Seok Kim, Samira Husen Alamudi, Young‐Tae Chang. ABCB1 Can Actively Pump‐out the Background‐Free Tame Fluorescent Probe CO‐1 From Live Cells. Chemistry – An Asian Journal 2022, 17 (12) https://doi.org/10.1002/asia.202200229
- Xiao Liu, Young-Tae Chang. Fluorescent probe strategy for live cell distinction. Chemical Society Reviews 2022, 51 (5) , 1573-1591. https://doi.org/10.1039/D1CS00388G
- Naoki Miyamoto, Young-Hyun Go, Larissa Miasiro Ciaramicoli, Haw-Young Kwon, Heon Seok Kim, Xuezhi Bi, Young Hyun Yu, Beomsue Kim, Hyung-Ho Ha, Nam-Young Kang, Seong-Wook Yun, Jin-Soo Kim, Hyuk-Jin Cha, Young-Tae Chang. Target identification of mouse stem cell probe CDy1 as ALDH2 and Abcb1b through live-cell affinity-matrix and ABC CRISPRa library. RSC Chemical Biology 2021, 2 (6) , 1590-1593. https://doi.org/10.1039/D1CB00147G
- Min Gao, Sun Hyeok Lee, Sang Hyuk Park, Larissa Miasiro Ciaramicoli, Haw‐Young Kwon, Heewon Cho, Joseph Jeong, Young‐Tae Chang. Neutrophil‐Selective Fluorescent Probe Development through Metabolism‐Oriented Live‐Cell Distinction. Angewandte Chemie 2021, 133 (44) , 23936-23942. https://doi.org/10.1002/ange.202108536
- Min Gao, Sun Hyeok Lee, Sang Hyuk Park, Larissa Miasiro Ciaramicoli, Haw‐Young Kwon, Heewon Cho, Joseph Jeong, Young‐Tae Chang. Neutrophil‐Selective Fluorescent Probe Development through Metabolism‐Oriented Live‐Cell Distinction. Angewandte Chemie International Edition 2021, 60 (44) , 23743-23749. https://doi.org/10.1002/anie.202108536
- Wenjie Lang, Chaonan Yuan, Liquan Zhu, Shubo Du, Linghui Qian, Jingyan Ge, Shao Q. Yao. Recent advances in construction of small molecule-based fluorophore-drug conjugates. Journal of Pharmaceutical Analysis 2020, 10 (5) , 434-443. https://doi.org/10.1016/j.jpha.2020.08.006
- Claire Wen Ying Neo, Larissa Miasiro Ciaramicoli, Andreas Alvin Purnomo Soetedjo, Adrian Kee Keong Teo, Nam-Young Kang. A new perspective of probe development for imaging pancreatic beta cell in vivo. Seminars in Cell & Developmental Biology 2020, 103 , 3-13. https://doi.org/10.1016/j.semcdb.2020.01.009