Pillar[6]arene acts as a biosensor for quantitative detection of a vitamin metabolite in crude biological samples

• Published in: Communications chemistry 2020-12, Vol.3 (1), p.183-183, Article 183
• Main Authors: Ueno, Masaya, Tomita, Takuya, Arakawa, Hiroshi, Kakuta, Takahiro, Yamagishi, Tada-aki, Terakawa, Jumpei, Daikoku, Takiko, Horike, Shin-ichi, Si, Sha, Kurayoshi, Kenta, Ito, Chiaki, Kasahara, Atsuko, Tadokoro, Yuko, Kobayashi, Masahiko, Fukuwatari, Tsutomu, Tamai, Ikumi, Hirao, Atsushi, Ogoshi, Tomoki
• Format: Article
• Language: English
• Subjects: 631/45; 639/638/45; 639/638/45/320; 639/638/45/56; 639/638/541; 96/33; Aromatic compounds; Biological properties; Biosensors; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Electron transfer; Hypertension; Metabolic disorders; Metabolites; Nicotinamide; Supramolecular compounds; Water chemistry
• ISSN: 2399-3669; 2399-3669
• DOI: 10.1038/s42004-020-00430-w

Metabolic syndrome is associated with obesity, hypertension, and dyslipidemia, and increased cardiovascular risk. Therefore, quick and accurate measurements of specific metabolites are critical for diagnosis; however, detection methods are limited. Here we describe the synthesis of pillar[n]arenes to target 1-methylnicotinamide (1-MNA), which is one metabolite of vitamin B3 (nicotinamide) produced by the cancer-associated nicotinamide N -methyltransferase (NNMT). We found that water-soluble pillar[5]arene (P5A) forms host–guest complexes with both 1-MNA and nicotinamide, and water-soluble pillar[6]arene (P6A) selectively binds to 1-MNA at the micromolar level. P6A can be used as a “turn-off sensor” by photoinduced electron transfer (detection limit is 4.38 × 10 −6  M). In our cell-free reaction, P6A is used to quantitatively monitor the activity of NNMT. Moreover, studies using NNMT-deficient mice reveal that P6A exclusively binds to 1-MNA in crude urinary samples. Our findings demonstrate that P6A can be used as a biosensor to quantify 1-MNA in crude biological samples. Quick and accurate measurements of specific metabolites are critical to diagnose certain pathological conditions, but quantification methods for relatively low molecular-weight metabolites are limited. Here, the water-soluble pillar[6]arene is used to specifically and quantitatively detect 1-methylnicotinamide in crude urinary samples.