Tietze, Lutz Friedjan

[["dc.bibliographiccitation.firstpage","134"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Toxins"],["dc.bibliographiccitation.lastpage","150"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","von Hof, J. Marian"],["dc.contributor.author","Frauendorf, Holm"],["dc.contributor.author","Schuberth, Ingrid"],["dc.date.accessioned","2018-11-07T11:21:49Z"],["dc.date.available","2018-11-07T11:21:49Z"],["dc.date.issued","2009"],["dc.description.abstract","The natural antibiotics CC-1065 and the duocarmycins are highly cytotoxic compounds which however are not suitable for cancer therapy due to their general toxicity. We have developed glycosidic prodrugs of seco-analogues of these antibiotics for a selective cancer therapy using conjugates of glycohydrolases and tumour-selective monoclonal antibodies for the liberation of the drugs from the prodrugs predominantly at the tumour site. For the determination of structure activity relationships of the different seco-drugs, experiments addressing their interaction with synthetic DNA were performed. Using electrospray mass spectrometry and high performance liquid chromatography, the experiments revealed a correlation of the stability of these drugs with their cytotoxicity in cell culture investigations. Furthermore, it was shown that the drugs bind to AT-rich regions of double-stranded DNA and the more cytotoxic drugs induce DNA fragmentation at room temperature in several of the selected DNA double-strands. Finally, an explanation for the very high cytotoxicity of CC-1065, the duocarmycins and analogous drugs is given."],["dc.identifier.doi","10.3390/toxins1020134"],["dc.identifier.isi","000208434400006"],["dc.identifier.pmid","22069536"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55867"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","2072-6651"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Determination of the Biological Activity and Structure Activity Relationships of Drugs Based on the Highly Cytotoxic Duocarmycins and CC-1065"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6921"],["dc.bibliographiccitation.issue","27"],["dc.bibliographiccitation.journal","Angewandte Chemie International Edition"],["dc.bibliographiccitation.lastpage","6925"],["dc.bibliographiccitation.volume","52"],["dc.contributor.author","Wirth, Tanja"],["dc.contributor.author","Pestel, Galina F."],["dc.contributor.author","Ganal, Vanessa"],["dc.contributor.author","Kirmeier, Thomas"],["dc.contributor.author","Schuberth, Ingrid"],["dc.contributor.author","Rein, Theo"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Sieber, Stephan A."],["dc.date.accessioned","2018-11-07T09:29:49Z"],["dc.date.available","2018-11-07T09:29:49Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1002/anie.201208941"],["dc.identifier.isi","000320776900020"],["dc.identifier.pmid","23681547"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31143"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1521-3773"],["dc.relation.issn","1433-7851"],["dc.title","The Two Faces of Potent Antitumor Duocarmycin-Based Drugs: A Structural Dissection Reveals Disparate Motifs for DNA versus Aldehyde Dehydrogenase1 Affinity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7336"],["dc.bibliographiccitation.issue","40"],["dc.bibliographiccitation.journal","Angewandte Chemie International Edition"],["dc.bibliographiccitation.lastpage","7339"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Tietze, Lutz F."],["dc.contributor.author","von Hof, J. Marian"],["dc.contributor.author","Mueller, Michael"],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","Schuberth, Ingrid"],["dc.date.accessioned","2018-11-07T08:46:59Z"],["dc.date.available","2018-11-07T08:46:59Z"],["dc.date.issued","2010"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft; Fonds der Chemischen Industrie"],["dc.identifier.doi","10.1002/anie.201002502"],["dc.identifier.isi","000282916800036"],["dc.identifier.pmid","20799305"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20829"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1433-7851"],["dc.title","Glycosidic Prodrugs of Highly Potent Bifunctional Duocarmycin Derivatives for Selective Treatment of Cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6570"],["dc.bibliographiccitation.issue","39"],["dc.bibliographiccitation.journal","Angewandte Chemie International Edition"],["dc.bibliographiccitation.lastpage","6574"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","Frauendorf, Holm"],["dc.contributor.author","Major, Felix"],["dc.contributor.author","Schuberth, Ingrid"],["dc.date.accessioned","2018-11-07T10:29:12Z"],["dc.date.available","2018-11-07T10:29:12Z"],["dc.date.issued","2006"],["dc.identifier.doi","10.1002/anie.200600935"],["dc.identifier.isi","000241314100037"],["dc.identifier.pmid","16960904"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43590"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1433-7851"],["dc.title","Investigation of reactivity and selectivity of DNA-alkylating duocarmycin analogues by high-resolution mass spectrometry"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2559"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Chemistry & Biodiversity"],["dc.bibliographiccitation.lastpage","2570"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Behrendt, Frank"],["dc.contributor.author","Pestel, Galina F."],["dc.contributor.author","Schuberth, Ingrid"],["dc.contributor.author","Mitkovski, Miso"],["dc.date.accessioned","2018-11-07T09:03:52Z"],["dc.date.available","2018-11-07T09:03:52Z"],["dc.date.issued","2012"],["dc.description.abstract","For a better understanding of the mode of action of duocarmycin and its analogs, the novel fluorescent duocarmycin derivatives 1315 and 17b19b were synthesized, and their bioactivity as well as their cellular uptake investigated using confocal laser scanning microscopy (CLSM) in live-cell imaging experiments."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft; Fonds der Chemischen Industrie"],["dc.identifier.doi","10.1002/cbdv.201200289"],["dc.identifier.isi","000311299400013"],["dc.identifier.pmid","23161634"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24985"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1612-1872"],["dc.title","Synthesis, Biological Evaluation, and Live Cell Imaging of Novel Fluorescent Duocarmycin Analogs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","425"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Heterocycles"],["dc.bibliographiccitation.lastpage","433"],["dc.bibliographiccitation.volume","86"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Heins, Arne"],["dc.contributor.author","Reiner, Johannes R."],["dc.contributor.author","Duefert, Svenia-C."],["dc.contributor.author","Schuberth, Ingrid"],["dc.date.accessioned","2018-11-07T09:02:08Z"],["dc.date.available","2018-11-07T09:02:08Z"],["dc.date.issued","2012"],["dc.description.abstract","The design of novel natural product hybrids consisting of parts of two or more bioactive compounds may allow an access to new drugs. Here we describe the synthesis of 3, a hybrid of the cytotoxic acronycine (2) and seco-duocarmycin (seco-1), which was prepared via a selective bromination of 7 followed by the introduction of an alkyne moiety, which was further manipulated to give the epoxide 12. Cyclisation and chlorination of the formed primary hydroxy group yielded 3, which in situ would give the desired hybrid 4. The in-vitro-cytotoxicity test revealed a slightly higher bioactivity of the hybrid 3 compared to acronycine (2)."],["dc.description.sponsorship","Konrad-Adenauer-Foundation"],["dc.identifier.doi","10.3987/COM-12-S(N)37"],["dc.identifier.isi","000313766800032"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24606"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0385-5414"],["dc.title","SYNTHESIS AND BIOLOGICAL EVALUATION OF A NOVEL ACRONYCINE/DUOCARMYCIN HYBRID NATURAL PRODUCT"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","537"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Medicinal Chemistry"],["dc.bibliographiccitation.lastpage","543"],["dc.bibliographiccitation.volume","52"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Schuster, Heiko J."],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","Schuberth, Ingrid"],["dc.date.accessioned","2018-11-07T08:33:27Z"],["dc.date.available","2018-11-07T08:33:27Z"],["dc.date.issued","2009"],["dc.description.abstract","The synthesis and biological evaluation of novel prodrugs for use in the antibody directed enzyme prodrug therapy (ADEPT) of cancer based on the cytotoxic antibiotic duocarmycin SA (1) are described. In this approach, we investigated the influence of the sugar moiety of the glycosidic prodrug on the QIC(50) values as well as on the stability and the water solubility. The best result was found for prodrug 22 containing an alpha-mannoside moiety with a QIC(50) value of 4500."],["dc.identifier.doi","10.1021/jm8009102"],["dc.identifier.isi","000262522100033"],["dc.identifier.pmid","19143570"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17582"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","0022-2623"],["dc.title","Synthesis and Biological Studies of Different Duocarmycin Based Glycosidic Prodrugs for Their Use in the Antibody-Directed Enzyme Prodrug Therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","13031"],["dc.bibliographiccitation.issue","36"],["dc.bibliographiccitation.journal","Journal of the American Chemical Society"],["dc.bibliographiccitation.lastpage","13036"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","Major, Felix"],["dc.contributor.author","Schuberth, Ingrid"],["dc.date.accessioned","2018-11-07T11:24:15Z"],["dc.date.available","2018-11-07T11:24:15Z"],["dc.date.issued","2009"],["dc.description.abstract","Circular dichroism (CD) spectroscopy is a well-known method for the analysis of chiral chemical compounds and is often used for studying the structure and interaction of proteins, DNA and bioactive compounds in solution. Here we demonstrate that CD spectroscopy is also a powerful tool for investigating the cellular uptake and mode of action of drugs in live cells. By means of CD spectroscopy, we identified DNA as the cellular target of several novel anticancer agents based on the highly cytotoxic natural antibiotic CC-1065. Furthermore, time-dependent changes in the CD spectra of drug-treated cells enabled us to rationalize differences in drug cytotoxicity. The anticancer agents rapidly penetrate the cell membrane and bind to cellular DNA as their intracellular target. Thereby, the formation of a reversible noncovalent complex with the DNA is followed by a covalent binding of the drugs to the DNA and the more toxic compounds show a higher stability and a lower alkylation rate. Since no drug manipulation is necessary for this kind of investigation and achiral compounds bound to chiral biomolecules may also show induced CD signals, CD spectroscopy of live cells is not limited to the study of analogues of CC-1065. Thus, it constitutes a general approach for studying the mode of action of bioactive compounds on the cellular and molecular level."],["dc.identifier.doi","10.1021/ja902767f"],["dc.identifier.isi","000269736000041"],["dc.identifier.pmid","19697908"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56358"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Chemical Soc"],["dc.relation.issn","0002-7863"],["dc.title","CD-Spectroscopy As a Powerful Tool for Investigating the Mode of Action of Unmodified Drugs in Live Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4563"],["dc.bibliographiccitation.issue","27"],["dc.bibliographiccitation.journal","European Journal of Organic Chemistry"],["dc.bibliographiccitation.lastpage","4577"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Gericke, Kersten M."],["dc.contributor.author","Schuberth, Ingrid"],["dc.date.accessioned","2018-11-07T10:58:58Z"],["dc.date.available","2018-11-07T10:58:58Z"],["dc.date.issued","2007"],["dc.description.abstract","Highly functionalized anthraquinones which derive from the natural products mensacarcin, islandicin, and chrysophanol have been efficiently synthesized using a Diels-Alder reaction as key step. The introduction of the proposed pharmaco-phoric side chain unit has been achieved by an addition of an aryllithimn species onto different aldehydes. Furthermore, the antitumor activity of these novel compounds has been studied by the in vitro growth inhibition of human lung carcinoma cells of line A549. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)."],["dc.identifier.doi","10.1002/ejoc.200700418"],["dc.identifier.isi","000249797700017"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50588"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1434-193X"],["dc.title","Synthesis of highly functionalized anthraquinones and evaluation of their antitumor activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1833"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Organic & Biomolecular Chemistry"],["dc.bibliographiccitation.lastpage","1842"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Schuster, Heiko J."],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","von Hof, J. Marian"],["dc.contributor.author","Schmuck, Kianga"],["dc.contributor.author","Schuberth, Ingrid"],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.date.accessioned","2018-11-07T08:48:20Z"],["dc.date.available","2018-11-07T08:48:20Z"],["dc.date.issued","2010"],["dc.description.abstract","The synthesis of the first spacer containing, duocarmycin analogue prodrug 11 was realised, its biological properties evaluated and compared to its counterpart prodrug 2 without a spacer unit. The synthesis comprises the manufacture of the new acetylated derivatives 19 and 20b of two double spacer systems, their activation and coupling to the pharmacophoric seco-drug (+)-3. Unprecedented biological results were found as the new prodrug 11 showed a fairly low QIC(50) value of 20, but on the other hand a high stability and very low DNA alkylation efficiency. These findings indicate a changed cytostatic mode of action induced by the self-immolative spacer moiety which was employed."],["dc.identifier.doi","10.1039/b925070k"],["dc.identifier.isi","000276192100014"],["dc.identifier.pmid","20449487"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21178"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Royal Soc Chemistry"],["dc.relation.issn","1477-0520"],["dc.title","Synthesis of the first spacer containing prodrug of a duocarmycin analogue and determination of its biological activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]