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Maurer B, Rumpf T, Scharfe M, et al. Inhibitors of the NAD(+)-Dependent Protein Desuccinylase and Demalonylase Sirt5. ACS Med Chem Lett. 2012;3(12):1050-3doi: 10.1021/ml3002709.
Maurer, B., Rumpf, T., Scharfe, M., Stolfa, D. A., Schmitt, M. L., He, W., Verdin, E., Sippl, W., & Jung, M. (2012). Inhibitors of the NAD(+)-Dependent Protein Desuccinylase and Demalonylase Sirt5. ACS medicinal chemistry letters, 3(12), 1050-3. https://doi.org/10.1021/ml3002709
Maurer, Benjamin, et al. "Inhibitors of the NAD(+)-Dependent Protein Desuccinylase and Demalonylase Sirt5." ACS medicinal chemistry letters vol. 3,12 (2012): 1050-3. doi: https://doi.org/10.1021/ml3002709
Maurer B, Rumpf T, Scharfe M, Stolfa DA, Schmitt ML, He W, Verdin E, Sippl W, Jung M. Inhibitors of the NAD(+)-Dependent Protein Desuccinylase and Demalonylase Sirt5. ACS Med Chem Lett. 2012 Oct 06;3(12):1050-3. doi: 10.1021/ml3002709. eCollection 2012 Dec 13. PMID: 24900427; PMCID: PMC4025838.
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ACS Med Chem Lett. 2012 Oct 06;3(12):1050-3. doi: 10.1021/ml3002709. eCollection 2012 Dec 13.

Inhibitors of the NAD(+)-Dependent Protein Desuccinylase and Demalonylase Sirt5.

ACS medicinal chemistry letters

Benjamin Maurer, Tobias Rumpf, Michael Scharfe, Diana A Stolfa, Martin L Schmitt, Wenjuan He, Eric Verdin, Wolfgang Sippl, Manfred Jung

Affiliations

  1. Institute of Pharmaceutical Sciences, Albert-Ludwigs Universität , Albertstrasse 25, 79104 Freiburg, Germany.
  2. Department of Pharmaceutical Chemistry, Martin-Luther Universität Halle-Wittenberg , Universitätsplatz 7, 06120 Halle/Saale, Germany.
  3. Gladstone Institute of Virology and Immunology , 1650 Owens Street, San Francisco, California 94158, United States.

PMID: 24900427 PMCID: PMC4025838 DOI: 10.1021/ml3002709

Abstract

NAD(+)-dependent histone deacetylases (sirtuins) play important roles in epigenetic regulation but also through nonhistone substrates for other key cellular events and have been linked to the pathogenesis of cancer, neurodegeneration, and metabolic diseases. The subtype Sirt5 has been shown recently to act as a desuccinylating and demalonylating enzyme. We have established an assay for biochemical testing of Sirt5 using a small labeled succinylated lysine derivative. We present a comparative study on the profiling of several established sirtuin inhibitors on Sirt1-3 as well as Sirt5 and also present initial results on a screening for new compounds that block Sirt5. Thiobarbiturates were identified as new Sirt5 inhibitors in the low micromolar range, which are selective over Sirt3 that can be found in the same cell compartment as Sirt5.

Keywords: AMC assay; Sirt5; desuccinylation; sirtinol; sirtuin

References

  1. Aging (Albany NY). 2011 Sep;3(9):829-35 - PubMed
  2. Mol Cell Proteomics. 2011 Dec;10(12):M111.012658 - PubMed
  3. Nature. 2003 Sep 11;425(6954):191-6 - PubMed
  4. Science. 2011 Nov 11;334(6057):806-9 - PubMed
  5. Biochem Biophys Res Commun. 1999 Jun 24;260(1):273-9 - PubMed
  6. J Med Chem. 2006 Dec 14;49(25):7307-16 - PubMed
  7. Structure. 2008 Sep 10;16(9):1368-77 - PubMed
  8. Cancer Res. 2006 Apr 15;66(8):4368-77 - PubMed
  9. Biochim Biophys Acta. 2010 Oct-Dec;1799(10-12):726-39 - PubMed
  10. ACS Chem Biol. 2012 Jan 20;7(1):155-9 - PubMed
  11. Cell Metab. 2011 Dec 7;14(6):718-9 - PubMed
  12. Cell. 2006 Sep 8;126(5):941-54 - PubMed
  13. J Med Chem. 2004 Oct 7;47(21):5235-43 - PubMed
  14. Structure. 2007 Mar;15(3):377-89 - PubMed
  15. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3651-6 - PubMed
  16. Biochemistry. 2007 Dec 18;46(50):14478-86 - PubMed
  17. J Biol Chem. 2001 Oct 19;276(42):38837-43 - PubMed
  18. J Am Chem Soc. 2012 Feb 1;134(4):1922-5 - PubMed
  19. Cell. 1999 Dec 23;99(7):735-45 - PubMed
  20. Methods. 2005 Aug;36(4):332-7 - PubMed
  21. J Med Chem. 2008 Mar 13;51(5):1203-13 - PubMed
  22. J Med Chem. 2005 Dec 15;48(25):8045-54 - PubMed
  23. J Med Chem. 2012 Jun 14;55(11):5582-90 - PubMed

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