Tobias Rumpf

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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(More)
Class III histone deacetylases (sirtuins) play pivotal roles in many cellular processes. They are linked to extended lifespan and to the pathogenesis of cancer and neuronal disorders. We present novel sirtuin inhibitors based on a 6,7-dichloro-2-oxindole scaffold with low micromolar activity. In vitro activity was rationalized by docking studies, and(More)
BACKGROUND Epigenetics is defined as heritable changes in gene expression that are not based on changes in the DNA sequence. Posttranslational modification of histone proteins is a major mechanism of epigenetic regulation. The kinase PRK1 (protein kinase C related kinase 1, also known as PKN1) phosphorylates histone H3 at threonine 11 and is involved in the(More)
Histone deacetylases (HDACs) are enzymes that cleave acetyl groups from acetyl-lysine residues in histones and various nonhistone proteins. Unlike the other three of the four classes of HDACs that have been identified in humans, which are zinc-dependent amidohydrolases, class III HDACs depend on nicotinamide adenine dinucleotide (NAD(+)) for their catalytic(More)
Involuntary commitment appears to be an infrequently used intervention with anorexic patients, in part because of clinicians' uncertainty about its applicability to this population. In contrast to overtly suicidal patients, anorexic patients typically fail to express an intent to harm themselves, although their actions may result in severe harm. Examination(More)
We report the design and concise synthesis, in two steps from commercially available material, of novel, bioactive derivatives of the enzyme cofactor nicotinamide adenine dinucleotide (NAD). The new synthetic dinucleotides act as sirtuin (SIRT) inhibitors and show isoform selectivity for SIRT2 over SIRT1. An NMR-based conformational analysis suggests that(More)
Protein kinase C Related Kinase 1 (PRK1) has been shown to be involved in the regulation of androgen receptor signaling and has been identified as a novel potential drug target for prostate cancer therapy. Since there is no PRK1 crystal structure available to date, multiple PRK1 homology models were generated in order to address the protein flexibility. An(More)
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(More)
Sirtuins are NAD(+)-dependent protein deacylases that cleave off acetyl groups, as well as other acyl groups, from the ɛ-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, thus making Sirt2 a promising target for(More)