15N-enriched NAD+/ NADH Analogs as Redox-Responsive MRI Sensors
Emily Buchanan1,2,3, James Ratnakar1, Eul Hyun Suh1, Jun Chen1, Ivan Dimitrov1,4, Jae Mo Park1, A. Dean Sherry1,2, and Zoltan Kovacs1
1Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States, 2Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX, United States, 3Physical Measurement Laboratory, National Institute of Standards and Technology, Boulder, CO, United States, 4Phillips Medical Systems, Cleveland, OH, United States
In this study, we prepared a 15N-enriched analog of NAD+ (N-methyl nicotinamide = MNA+) and demonstrated that it undergoes reduction by sodium dithionate to form MNAH. The 15N chemical shifts of the oxidized and reduced forms differ by 124.2ppm. DNP of MNA+ followed by dissolution and 15N NMR showed a favorable T1 relaxation time of 130s at 1T and 50s at 3T. Deuteration of the methyl protons only increased the T1 of 15N by ~10s. The long T1 of 15N in these NAD+/NADH mimetics and the large chemical shift difference offer the exciting potential for their use as redox sensors.
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