Abstract
Nuclear magnetic resonance (NMR)-based screening has been recognized as a powerful approach for the identification and characterization of molecules interacting with pharmaceutical targets. Indeed, several NMR methods have been developed and successfully applied to many drug discovery projects. Whereas most of these approaches have targeted isolated biomolecular receptors, very few cases are reported with the screening performed in intact cells and cell extracts. Here we report the first successful application of the fluorine NMR-based assay n-FABS (n-fluorine atoms for biochemical screening) in living mammalian cells expressing the membrane protein fatty acid amide hydrolase (FAAH). This method allows the identification of both weak and potent inhibitors and the measurement of their potency in a physiological environment.
Highlights
Marina Veronesi a, *, Francesca Giacomina a, Elisa Romeo a, Beatrice Castellani a, Giuliana Ottonello a, Chiara Lambruschini a, 1, Gianpiero Garau a, Rita Scarpelli a, Tiziano Bandiera a, Daniele Piomelli a, b, Claudio Dalvit c, **
Its robustness and sensitivity have prompted its application in several drug discovery projects in both academia and industry [18]. n-fluorine atoms for biochemical screening (n-FABS) has been successfully used for the identification of inhibitors of different enzymes [19e25] and for the screening of natural extracts originated from traditional Chinese medicine [26]
We report the first application of n-FABS as a valuable screening method to identify inhibitors of human fatty acid amide hydrolase (FAAH) in intact mammalian living cells
Summary
Marina Veronesi a, *, Francesca Giacomina a, Elisa Romeo a, Beatrice Castellani a, Giuliana Ottonello a, Chiara Lambruschini a, 1, Gianpiero Garau a, Rita Scarpelli a, Tiziano Bandiera a, Daniele Piomelli a, b, Claudio Dalvit c, **. Several NMR methods have been developed and successfully applied to many drug discovery projects Whereas most of these approaches have targeted isolated biomolecular receptors, very few cases are reported with the screening performed in intact cells and cell extracts. We report the first successful application of the fluorine NMR-based assay n-FABS (n-fluorine atoms for biochemical screening) in living mammalian cells expressing the membrane protein fatty acid amide hydrolase (FAAH). This method allows the identification of both weak and potent inhibitors and the measurement of their potency in a physiological environment. These systems are those found in enzymatic pathways and, more generally, in system biology [14,21,27]
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