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

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 <i>N</i>-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<sup>6</sup> M<sup>-1</sup>, 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<sup>-7</sup> 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.

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Publication Details

Journal
Analytical Chemistry
Published
2024-08-26
DOI
https://doi.org/10.1021/acs.analchem.4c02653
Citations
2
Primary Topic
Molecular Sensors and Ion Detection
Type
article
Field-Weighted Citation Impact
0.48

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article

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

Kenjiro Ono, Atsuko Kasahara, Moeko Noguchi‐Shinohara, Feng Li et al.
2 citations
Analytical Chemistry
Molecular Sensors and Ion Detection
0.48
article

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

Kenjiro Ono, Atsuko Kasahara, Moeko Noguchi‐Shinohara, Feng Li, Atsushi Hirao, Tomoki Ogoshi, Atsushi Tajima, Yusuke Masuo, Hiroki Sugiyama, Mahmoud I. Shoulkamy, Kenta Kurayoshi, Tomoyoshi Soga, Shinji Takeuchi, Toshinari Takamura, Yukio Kato, Hiromasa Tsujiguchi, Tatsuya Nishimura, Masahiko Kobayashi, Masaya Ueno, Xiaoxiao Cheng, Katsuhiro Maeda, Sakae Miyagi, Akinori Hara, Hiroyuki Nakamura, Tadashi Toyama, Yumie Takeshita, Xi Chen, Yuko Tadokoro, Hiroshi Arakawa
article en
2 citations

Abstract

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 <i>N</i>-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<sup>6</sup> M<sup>-1</sup>, 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<sup>-7</sup> 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.

Analytical ChemistryVol. 96(36)
Kanazawa University (JP), University of Fukui (JP), Keio University (JP), Kyoto University (JP), Life Science Institute (JP), Minia University (EG)
Japan Agency for Medical Research and Development, Kanazawa University, Japan Science and Technology Corporation, Ministry of Education, Culture, Sports, Science and Technology
Openalex Percentile: Top 41%
Molecular Sensors and Ion Detection
0.48
DOISourceOpenAlex
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