Sirtuin 1 Inhibiting Thiocyanates (S1th)—A New Class of Isotype Selective Inhibitors of NAD+ Dependent Lysine Deacetylases
نویسندگان
چکیده
منابع مشابه
Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening.
The yeast transcriptional repressor Sir2p silences gene expression from the telomeric, rDNA, and silent mating-type loci and may play a role in higher order processes such as aging. Sir2p is the founding member of a large family of NAD-dependent deacetylase enzymes, named the sirtuins. These proteins are conserved from prokaryotes to eukaryotes, but most remain uncharacterized, including all se...
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each region through immunofluorescence, cross-linking Pacific Hall 0347 and chromatin immunoprecipitation, and biochemical 9500 Gilman Drive purification. SIR2 is not itself essential for viability, but La Jolla, California 92093 sir2⌬ null mutants have a number of phenotypes. In addition to transcriptional silencing defects, sir2⌬ strains have increased rates of recombination within Pundits an...
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Inhibitors of human NAD(+)-dependent protein deacetylases possess great value for deciphering the biology of these enzymes and as potential therapeutics for metabolic and age-related diseases and cancer. In the current study, we have experimentally demonstrated that, the potent inhibition we obtained previously for one of these enzymes (i.e. sirtuin type 1 (SIRT1)) by simply replacing N(epsilon...
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The class III lysine deacylases (KDACs), also known as the sirtuins, have emerged as interesting drug targets for therapeutic intervention in a variety of diseases. To gain a deeper understanding of the processes affected by sirtuins, the development of selective small molecule modulators of individual isozymes has been a longstanding goal. Essential for the discovery of novel modulators, howev...
متن کاملSelective Sirt2 inhibition by ligand-induced rearrangement of the active site
Sirtuins are a highly conserved class of NAD(+)-dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 activity a promising strategy for pharmaceutical intervention. A rational basis for the development of optimized Sirt2 inhibitors is lacking so far. Here we present high-res...
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ژورنال
عنوان ژورنال: Frontiers in Oncology
سال: 2020
ISSN: 2234-943X
DOI: 10.3389/fonc.2020.00657