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JFL, Lower Atrium

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This study investigates the impact of various molecules and their potential ability to act as allosteric modulators. Fatty acyl amide hydrolase (FAAH) is one of two main enzymes, along with monoacylglycerol lipase (MAGL), that break down endocannabinoids such as arachidonoyl ethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG). Endocannabinoids bind to cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) which expresses in our central nervous system. The expression of these endocannabinoids has been linked in contributing to pain relief, wound recovery, our immune system, and the function of many organs and bodily systems. A compound found to potentially modulate FAAH could have potential benefits. Three μM concentration of the compounds’, alpha tocopherol (alpha TOC), para hydroxybenzothioamide (4-HBTA), and benzoxaborole, ability to modulate the known FAAH inhibitor JZL-195’s activity was assessed in a FAAH inhibitor screening assay kit. The FAAH inhibitor screening assay kit assessed the FAAH catalyzed hydrolysis of AMC arachidonoyl amide and activity was determined by fluorescence. The fluorescence assay was run on the TECAN, and the inhibition curves were plotted using GraphPad Prism. Preliminary results indicate that alpha TOC is an allosteric modulator of FAAH. The positive results with alpha TOC were followed by enzyme kinetics studies. Future research would explore varying the concentration of substate AMC arachidonoyl amide to test the extent of the allosteric modulation from alpha TOC.

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Apr 16th, 1:00 PM

Allosteric Modulation of FAAH by Direct Compounds

JFL, Lower Atrium

This study investigates the impact of various molecules and their potential ability to act as allosteric modulators. Fatty acyl amide hydrolase (FAAH) is one of two main enzymes, along with monoacylglycerol lipase (MAGL), that break down endocannabinoids such as arachidonoyl ethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG). Endocannabinoids bind to cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) which expresses in our central nervous system. The expression of these endocannabinoids has been linked in contributing to pain relief, wound recovery, our immune system, and the function of many organs and bodily systems. A compound found to potentially modulate FAAH could have potential benefits. Three μM concentration of the compounds’, alpha tocopherol (alpha TOC), para hydroxybenzothioamide (4-HBTA), and benzoxaborole, ability to modulate the known FAAH inhibitor JZL-195’s activity was assessed in a FAAH inhibitor screening assay kit. The FAAH inhibitor screening assay kit assessed the FAAH catalyzed hydrolysis of AMC arachidonoyl amide and activity was determined by fluorescence. The fluorescence assay was run on the TECAN, and the inhibition curves were plotted using GraphPad Prism. Preliminary results indicate that alpha TOC is an allosteric modulator of FAAH. The positive results with alpha TOC were followed by enzyme kinetics studies. Future research would explore varying the concentration of substate AMC arachidonoyl amide to test the extent of the allosteric modulation from alpha TOC.

 

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