A Supramolecular Biosensor for Rapid and High-Throughput Quantification of a Disease-Associated Niacin Metabolite.

Autor: Ueno M; Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Sugiyama H; Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Li F; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Nishimura T; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Arakawa H; Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan., Chen X; Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Cheng X; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Takeuchi S; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; Division of Medical Oncology Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan., Takeshita Y; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan., Takamura T; Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan., Miyagi S; Innovative Clinical Research Center, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan., Toyama T; Innovative Clinical Research Center, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan.; Department of Nephrology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193, Japan., Soga T; Institute for Advanced Biosciences, Keio University, 246-2 Kakuganji-mizukami, Tsuruoka, Yamagata 997-0052, Japan., Masuo Y; Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan., Kato Y; Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan., Nakamura H; Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan., Tsujiguchi H; Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan., Hara A; Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan., Tajima A; Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan., Noguchi-Shinohara M; Department of Neurology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-1192, Japan., Ono K; Department of Neurology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, Ishikawa 920-1192, Japan., Kurayoshi K; Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Kobayashi M; Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Tadokoro Y; Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Kasahara A; Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; Institute for Frontier Science Initiative, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Shoulkamy MI; Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; Zoology Department, Faculty of Science, Minia University, El-Minia 61519, Egypt., Maeda K; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan., Ogoshi T; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan., Hirao A; Division of Molecular Genetics, Cancer and Stem Cell Research Program, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.; WPI Nano Life Science Institute (WPI-Nano LSI), Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
Jazyk: angličtina
Zdroj: Analytical chemistry [Anal Chem] 2024 Sep 10; Vol. 96 (36), pp. 14499-14507. Date of Electronic Publication: 2024 Aug 25.
DOI: 10.1021/acs.analchem.4c02653
Abstrakt: Metabolic abnormalities play a pivotal role in various pathological conditions, necessitating the quantification of specific metabolites for diagnosis. While mass spectrometry remains the primary method for metabolite measurement, its limited throughput underscores the need for biosensors capable of rapid detection. Previously, we reported that pillar[6]arene with 12 carboxylate groups (P6AC) forms host-guest complexes with 1-methylnicotinamide (1-MNA), which is produced in vivo by nicotinamide N -methyltransferase (NNMT). P6AC acts as a biosensor by measuring the fluorescence quenching caused by photoinduced electron transfer upon 1-MNA binding. However, the low sensitivity of P6AC makes it impractical for detecting 1-MNA in unpurified biological samples. In this study, we found that P6A with 12 sulfonate groups (P6AS) is a specific and potent supramolecular host for 1-MNA interactions even in biological samples. The 1-MNA binding affinity of P6AS in water was found to be (5.68 ± 1.02) × 10 6 M -1 , which is approximately 700-fold higher than that of P6AC. Moreover, the 1-MNA detection limit of P6AS was determined to be 2.84 × 10 -7 M, which is substantially lower than that of P6AC. Direct addition of P6AS to culture medium was sufficient to quantify 1-MNA produced by cancer cells. Furthermore, this sensor was able to specifically detect 1-MNA even in unpurified human urine. P6AS therefore enables rapid and high-throughput quantification of 1-MNA, and further improvement of our strategy will contribute to the establishment of high-throughput screening of NNMT inhibitors, diagnosis of liver diseases, and imaging of human cancer cells in vivo.
Databáze: MEDLINE
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