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Molecules 2012, 17(10), 12206-12224; doi:10.3390/molecules171012206
Article

Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a 1H-NMR Method to Assess Deacetylase Activity

1, 1, 1, 2, 2, 2, 3,4, 1 and 1,*
Received: 14 September 2012; in revised form: 21 September 2012 / Accepted: 15 October 2012 / Published: 18 October 2012
(This article belongs to the Special Issue Chemical Genetics)
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Abstract: The search for potent and selective sirtuin inhibitors continues as chemical tools of this type are of use in helping to assign the function of this interesting class of deacetylases. Here we describe SAR studies starting from the unselective sirtuin inhibitor tenovin-6. These studies identify a sub-micromolar inhibitor that has increased selectivity for SIRT2 over SIRT1 compared to tenovin-6. In addition, a 1H-NMR-based method is developed and used to validate further this class of sirtuin inhibitors. A thermal shift analysis of SIRT2 in the presence of tenovin-6, -43, a control tenovin and the known SIRT2 inhibitor AGK2 is also presented.
Keywords: sirtuin; chemical tool; deacetylase assay; neurodegenerative diseases sirtuin; chemical tool; deacetylase assay; neurodegenerative diseases
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Pirrie, L.; McCarthy, A.R.; Major, L.L.; Morkūnaitė, V.; Zubrienė, A.; Matulis, D.; Lain, S.; Lebl, T.; Westwood, N.J. Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a 1H-NMR Method to Assess Deacetylase Activity. Molecules 2012, 17, 12206-12224.

AMA Style

Pirrie L, McCarthy AR, Major LL, Morkūnaitė V, Zubrienė A, Matulis D, Lain S, Lebl T, Westwood NJ. Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a 1H-NMR Method to Assess Deacetylase Activity. Molecules. 2012; 17(10):12206-12224.

Chicago/Turabian Style

Pirrie, Lisa; McCarthy, Anna R.; Major, Louise L.; Morkūnaitė, Vaida; Zubrienė, Asta; Matulis, Daumantas; Lain, Sonia; Lebl, Tomas; Westwood, Nicholas J. 2012. "Discovery and Validation of SIRT2 Inhibitors Based on Tenovin-6: Use of a 1H-NMR Method to Assess Deacetylase Activity." Molecules 17, no. 10: 12206-12224.


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