Schwienhorst, Andreas

[["dc.bibliographiccitation.firstpage","202"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Analytical Biochemistry"],["dc.bibliographiccitation.lastpage","208"],["dc.bibliographiccitation.volume","321"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2021-06-01T10:50:01Z"],["dc.date.available","2021-06-01T10:50:01Z"],["dc.date.issued","2003"],["dc.identifier.doi","10.1016/S0003-2697(03)00426-3"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86498"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","0003-2697"],["dc.title","Improved fluorogenic histone deacetylase assay for high-throughput-screening applications"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","270"],["dc.bibliographiccitation.journal","Acta Crystallographica Section F Structural Biology and Crystallization Communications"],["dc.bibliographiccitation.lastpage","273"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Nielsen, Tine Kragh"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.contributor.author","Ficner, Ralf"],["dc.date.accessioned","2017-09-07T11:49:48Z"],["dc.date.available","2017-09-07T11:49:48Z"],["dc.date.issued","2007"],["dc.description.abstract","Histone deacetylases (HDACs) have emerged as attractive targets in anticancer drug development. To date, a number of HDAC inhibitors have been developed and most of them are hydroxamic acid derivatives, typified by suberoylanilide hydroxamic acid (SAHA). Not surprisingly, structural information that can greatly enhance the design of novel HDAC inhibitors is so far only available for hydroxamic acids in complex with HDAC or HDAC-like enzymes. Here, the first structure of an enzyme complex with a nonhydroxamate HDAC inhibitor is presented. The structure of the trifluoromethyl ketone inhibitor 9,9,9-trifluoro-8-oxo-N-phenylnonanamide in complex with bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from Bordetella/Alcaligenes strain FB188) has been determined. HDAH reveals high sequential and functional homology to human class 2 HDACs and a high structural homology to human class 1 HDACs. Comparison with the structure of HDAH in complex with SAHA reveals that the two inhibitors superimpose well. However, significant differences in binding to the active site of HDAH were observed. In the presented structure the O atom of the trifluoromethyl ketone moiety is within binding distance of the Zn atom of the enzyme and the F atoms participate in interactions with the enzyme, thereby involving more amino acids in enzyme-inhibitor binding."],["dc.identifier.doi","10.1107/S1744309107012377"],["dc.identifier.gro","3143512"],["dc.identifier.isi","000245505800004"],["dc.identifier.pmid","17401192"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1034"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","1744-3091"],["dc.title","Complex structure of a bacterial class 2 histone deacetylase homologue with a trifluoromethylketone inhibitor"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","267"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biochemical and Biophysical Research Communications"],["dc.bibliographiccitation.lastpage","272"],["dc.bibliographiccitation.volume","283"],["dc.contributor.author","Hempel, René"],["dc.contributor.author","Schmidt-Brauns, Joachim"],["dc.contributor.author","Gebinoga, Michael"],["dc.contributor.author","Wirsching, Frank"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2021-06-01T10:47:31Z"],["dc.date.available","2021-06-01T10:47:31Z"],["dc.date.issued","2001"],["dc.identifier.doi","10.1006/bbrc.2001.4766"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85630"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","0006-291X"],["dc.title","Cation Radius Effects on Cell-Free Translation in Rabbit Reticulocyte Lysate"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2773"],["dc.bibliographiccitation.issue","23"],["dc.bibliographiccitation.journal","Cellular and Molecular Life Sciences"],["dc.bibliographiccitation.lastpage","2791"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2018-11-07T09:00:09Z"],["dc.date.available","2018-11-07T09:00:09Z"],["dc.date.issued","2006"],["dc.description.abstract","Thrombin is a plasma serine protease that plays a key role in coagulation and hemostasis but also in thromboembolic diseases. Direct thrombin inhibitors could, therefore, be beneficial for future anticoagulant therapy in the prophylaxis of venous and arterial thrombosis as well as myocardial infarction. However, development of direct thrombin inhibitors has brought researchers more heartache than success. The most recent setback came this year when AstraZeneca withdrew Ximelagatran, the first orally bioavailable direct thrombin inhibitor that had received regulatory approval (France, 2003), after reports of serious hepatoxicity in a fraction of patients. This review describes the status of direct thrombin inhibitors, focusing on drug candidates that are at present in clinical trials. In addition, some more recent research strategies in the design of novel direct thrombin inhibitors are discussed, which may very well contribute to future developments of potent anticoagulants."],["dc.identifier.doi","10.1007/s00018-006-6219-z"],["dc.identifier.isi","000242813800008"],["dc.identifier.pmid","17103113"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24080"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Birkhauser Verlag Ag"],["dc.relation.issn","1420-682X"],["dc.title","Direct thrombin inhibitors - a survey of recent developments"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2011"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Bioorganic & Medicinal Chemistry"],["dc.bibliographiccitation.lastpage","2033"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Schaefer, Stefan"],["dc.contributor.author","Saunders, Laura"],["dc.contributor.author","Eliseeva, Elena"],["dc.contributor.author","Velena, Alfredo"],["dc.contributor.author","Jung, Mira"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.contributor.author","Strasser, Anja"],["dc.contributor.author","Dickmanns, Achim"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Schlimme, Sonja"],["dc.contributor.author","Sippl, Wolfgang"],["dc.contributor.author","Verdin, Eric"],["dc.contributor.author","Jung, Manfred"],["dc.date.accessioned","2017-09-07T11:48:47Z"],["dc.date.available","2017-09-07T11:48:47Z"],["dc.date.issued","2008"],["dc.description.abstract","We synthesized biarylalanine-containing hydroxamic acids and tested them on immunoprecipitated HDAC1 and HDAC6 and show a subtype selectivity for HDAC6 that was confirmed in cells by Western blot (tubulin vs histones). We obtained an X-ray structure with a HDAC6-selective inhibitor with the bacterial deacetylase HDAH. Docking studies were carried out using HDAC1 and HDAC6 protein models. Antiproliferative activity was shown on cancer cells for selected compounds. (c) 2007 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.bmc.2007.10.092"],["dc.identifier.gro","3143345"],["dc.identifier.isi","000254080900037"],["dc.identifier.pmid","18054239"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/849"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0968-0896"],["dc.title","Phenylalanine-containing hydroxamic acids as selective inhibitors of class IIb histone deacetylases (HDACs)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5784"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Journal of Virology"],["dc.bibliographiccitation.lastpage","5792"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Lindemann, B. F."],["dc.contributor.author","Klug, C."],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2018-11-07T10:29:10Z"],["dc.date.available","2018-11-07T10:29:10Z"],["dc.date.issued","2002"],["dc.description.abstract","The emergence of viral escape mutants is usually a highly undesirable phenomenon. This phenomenon is frequently observed in antiviral drug applications for the treatment of viral infections and can undermine long-term therapeutic success. Here, we propose a strategy for evaluating a given antiviral approach in terms of its potential to provoke the appearance of resistant virus mutants. By use of Q(3 RNA phage as a model system, the effect of an antiviral gene therapy, i.e., a virus-specific repressor protein expressed by a recombinant Escherichia coli host, was studied over the course of more than 100 generations. In 13 experiments carried out in parallel, 12 phage populations became resistant and 1 became extinct. Sequence analysis revealed that only two distinct phage mutants emerged in the 12 surviving phage populations. For both escape mutants, sequence variations located in the repressor binding site of the viral genomic RNA, which decrease affinity for the repressor protein, conferred resistance to translational repression. The results clearly suggest the feasibility of the proposed strategy for the evaluation of antiviral approaches in terms of their potential to allow resistant mutants to appear. In addition, the strategy proved to be a valuable tool for observing virus-specific molecular targets under the impact of antiviral drugs."],["dc.identifier.doi","10.1128/JVI.76.11.5784-5792.2002"],["dc.identifier.isi","000175546000049"],["dc.identifier.pmid","11992006"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43585"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","1098-5514"],["dc.relation.issn","0022-538X"],["dc.title","Evolution of bacteriophage in continuous culture: a model system to test antiviral gene therapies for the emergence of phage escape mutants"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","451"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Molecular Genetics and Metabolism"],["dc.bibliographiccitation.lastpage","462"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Wirsching, Frank"],["dc.contributor.author","Keller, Martina"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2021-06-01T10:50:00Z"],["dc.date.available","2021-06-01T10:50:00Z"],["dc.date.issued","2003"],["dc.identifier.doi","10.1016/j.ymgme.2003.09.007"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86486"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.issn","1096-7192"],["dc.title","Directed evolution towards protease-resistant hirudin variants"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3651"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Bioorganic & Medicinal Chemistry Letters"],["dc.bibliographiccitation.lastpage","3656"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Haus, Patricia"],["dc.contributor.author","Galetovic, Antonia"],["dc.contributor.author","Schober, Andreas"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.contributor.author","Meyer-Almes, Franz-Josef"],["dc.date.accessioned","2018-11-07T08:28:00Z"],["dc.date.available","2018-11-07T08:28:00Z"],["dc.date.issued","2009"],["dc.description.abstract","Histone deacetylases reside among the most important and novel target classes in oncology. Selective lead structures are intensively developed to improve efficacy and reduce adverse effects. The common assays used so far to identify new lead structures suffer from many false positive hits due to auto-fluorescence of compounds or triggering undesired signal transduction pathways. These drawbacks are eliminated by the dual parameter competition assay reported in this study. The assay involves a new fluorescent inhibitor probe that shows an increase in both, fluorescence anisotropy and fluorescence lifetime upon binding to the enzyme. The assay is well suited for high-throughput screening. (C) 2009 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.bmcl.2009.04.102"],["dc.identifier.isi","000266822800064"],["dc.identifier.pmid","19457659"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16324"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","1464-3405"],["dc.relation.issn","0960-894X"],["dc.title","Non-isotopic dual parameter competition assay suitable for high-throughput screening of histone deacetylases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","439"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biochemical and Biophysical Research Communications"],["dc.bibliographiccitation.lastpage","445"],["dc.bibliographiccitation.volume","357"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Gruenewald, Sylvia"],["dc.contributor.author","Beckers, Thomas"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2018-11-07T11:01:37Z"],["dc.date.available","2018-11-07T11:01:37Z"],["dc.date.issued","2007"],["dc.description.abstract","Historic deacetylases (HDACs) catalyze the deacetylation of epsilon-acetyl-lysine residues within the N-terminal tail of core histones and thereby mediate changes in the chromatin structure and regulate gene expression in eukaryotic cells. So far, surprisingly little is known about the substrate specificities of different HDACs. Here, we prepared a library of fluorogenic tripeptidic substrates of the general format Ac-P-2-P-1-Lys(Ac)-MCA (P-1, P-2 = all amino acids except cysteine) and measured their HDAC-dependent conversion in a standard fluorogenic HDAC assay. Different HDAC subtypes can be ranked according to their substrate selectivity: HDAH > HDAC8 > HDAC1 > HDAC3 > HDAC6. HDAC1, HDAC3, and HDAC6 exhibit a similar specificity profile, whereas both HDAC8 and HDAH have rather distinct profiles. Furthermore, it was shown that second-site modification (e.g., phosphorylation) of substrate sequences as well as corepressor binding can modulate the selectivity of enzymatic substrate conversion. (c) 2007 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.bbrc.2007.03.158"],["dc.identifier.isi","000246253700019"],["dc.identifier.pmid","17428445"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51188"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","0006-291X"],["dc.title","Factors affecting the substrate specificity of histone deacetylases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","258"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.lastpage","270"],["dc.bibliographiccitation.volume","124"],["dc.contributor.author","Hildmann, Christian"],["dc.contributor.author","Wegener, Dennis"],["dc.contributor.author","Riester, Daniel"],["dc.contributor.author","Hempel, Rene"],["dc.contributor.author","Schober, Andreas"],["dc.contributor.author","Merana, Joachim"],["dc.contributor.author","Giurato, Laura"],["dc.contributor.author","Guccione, Salvatore"],["dc.contributor.author","Nielsen, Tine Kragh"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Schwienhorst, Andreas"],["dc.date.accessioned","2017-09-07T11:52:42Z"],["dc.date.available","2017-09-07T11:52:42Z"],["dc.date.issued","2006"],["dc.description.abstract","Histone deacetylases (HDACs) are key enzymes in the transcriptional regulation of gene expression in eukaryotic cells. In recent years MACs have attracted considerable attention as promising new targets in anticancer therapy. Currently, different histone deacetylase subtypes are divided into four groups denoted as classes 1-4. Here, we compare in more detail representatives of class I HDACs and FB188 HDAH as a close bacterial homologue of class 2 HDAC6, in regard of substrate and inhibitor specificity. Structure comparison is used to identify candidate regions responsible for observed specificity differences. Knowledge of these structural elements expedite studies on the biochemical role of different HDAC subtypes as well as the development of highly selective HDAC inhibitors as antitumor agents. (c) 2006 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jbiotec.2006.01.030"],["dc.identifier.gro","3143672"],["dc.identifier.isi","000238620900022"],["dc.identifier.pmid","16567013"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1211"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eissn","1873-4863"],["dc.relation.eventlocation","Wiesbaden, GERMANY"],["dc.relation.ispartof","Journal of Biotechnology"],["dc.relation.issn","0168-1656"],["dc.title","Substrate and inhibitor specificity of class 1 and class 2 histone deacetylases"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]