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","6909"],["dc.bibliographiccitation.issue","36"],["dc.bibliographiccitation.journal","European Journal of Organic Chemistry"],["dc.bibliographiccitation.lastpage","6921"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Behrendt, Frank"],["dc.contributor.author","Major, Felix"],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","von Hof, J. Marian"],["dc.date.accessioned","2018-11-07T08:36:11Z"],["dc.date.available","2018-11-07T08:36:11Z"],["dc.date.issued","2010"],["dc.description.abstract","The synthesis of the glycosidic prodrugs (1S)-30a, (1S,10R)-30b and (1S,10R)-32 labelled with different fluorescence dyes at different positions at the aromatic A-ring in 2 is described; the compounds are structurally based on the cytotoxic antibiotic duocarmycin SA. For binding, the amino compounds (1S)-3a and (1S,10R)-3b were treated with the commercially available succinimides of the dyes 5-SFX (29) and D10162 (31), respectively."],["dc.identifier.doi","10.1002/ejoc.201000966"],["dc.identifier.isi","000285311000005"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18251"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1434-193X"],["dc.title","Synthesis of Fluorescence-Labelled Glycosidic Prodrugs Based on the Cytotoxic Antibiotic Duocarmycin"],["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","437"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Analytical and Bioanalytical Chemistry"],["dc.bibliographiccitation.lastpage","448"],["dc.bibliographiccitation.volume","395"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","Frauendorf, Holm"],["dc.date.accessioned","2018-11-07T11:24:30Z"],["dc.date.available","2018-11-07T11:24:30Z"],["dc.date.issued","2009"],["dc.description.abstract","One of the main problems of anti-cancer therapy is an insufficient differentiation between normal and malignant cells by the known anti-proliferant agents. The antibody-directed enzyme prodrug therapy is a promising approach for a selective treatment of cancer, in which a non-toxic prodrug is enzymatically converted into a highly cytotoxic drug at the surface of malignant cells by a targeted antibody-enzyme conjugate. The transformations and the stability of a very promising novel prodrug and its corresponding cytotoxic derivative were now investigated in detail by high-performance liquid chromatography (HPLC)-mass spectrometry (MS). In order to determine the time-dependent DNA alkylation efficiency and the sequence selectivity of the novel compounds, DNA binding studies using direct electrospray-Fourier transform ion cyclotron resonance-MS (ESI-FTICR-MS) have been performed. These measurements were accompanied by HPLC analyses followed by MS of the separated species to confirm the results of the direct ESI-FTICR-MS measurements. The sites of DNA alkylation could be identified unambiguously by the mass spectrometric fragmentation pattern of the alkylated oligodeoxynucleotides as well as by the results of HPLC followed by MS. A combination of all techniques applied led to a better understanding of the mode of action of the new therapeutics and might be used for an estimation of the cytotoxicity of different prodrugs and drugs since the alkylation efficiency correlates with the bioactivity of the compounds in cell culture investigations."],["dc.identifier.doi","10.1007/s00216-009-2963-x"],["dc.identifier.isi","000269006500020"],["dc.identifier.pmid","19641906"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?goescholar/3483"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56421"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.conference","27th International Symposium on Chromatography"],["dc.relation.eventlocation","Munster, GERMANY"],["dc.relation.issn","1618-2642"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Investigation of the transformations of a novel anti-cancer agent combining HPLC, HPLC-MS and direct ESI-HRMS analyses"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["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","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"]]

[["dc.bibliographiccitation.firstpage","661"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","European Journal of Mass Spectrometry"],["dc.bibliographiccitation.lastpage","672"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","Frauendorf, Holm"],["dc.date.accessioned","2018-11-07T08:34:26Z"],["dc.date.available","2018-11-07T08:34:26Z"],["dc.date.issued","2009"],["dc.description.abstract","Treating cancer without harming healthy tissue is an important goat in modern medicine. Our research group has developed a series of novel, relatively non-toxic glycosidic prodrugs that are activated to give the corresponding highly cytotoxic drugs selectively in the tumour tissue. Our first investigations have shown a high duplex DNA alkylation efficiency of the drugs, whereas the prodrugs showed almost no tendency for alkylation of duplex DNA. Herein we report on novel investigations of the mode of action of the anti-cancer drugs on a molecular level. Using high-resolution mass spectrometry, we determined the reactivity of these drugs as well as of other drugs of similar structure against different nucleophiles such as RNA and the tripeptide glutathione. In addition, the new drugs were also tested for their interaction with duplex DNA. All compounds show a high reactivity against duplex DNA, whereas the alkylation efficiency regarding RNA and glutathione is only poor. Furthermore, the alkylation of duplex DNA correlates qualitatively but not quantitatively with the cytotoxicity of the drugs. Consequently, other factors besides the alkylation efficiency such as the stability of the drugs seem to influence their biological activity. Altogether the results show that high-resolution mass spectrometry constitutes a powerful method for studying the mode of action of drugs on a molecular level."],["dc.identifier.doi","10.1255/ejms.1021"],["dc.identifier.isi","000269650000011"],["dc.identifier.pmid","19679946"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17811"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Im Publications"],["dc.relation.issn","1469-0667"],["dc.title","Probing the mechanism of action of potential anticancer agents at a molecular level using electrospray ionisation Fourier transform ion cyclotron resonance 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","821"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.lastpage","837"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Panknin, Olaf"],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","Major, Felix"],["dc.contributor.author","Schuberth, Ingrid"],["dc.date.accessioned","2018-11-07T11:15:34Z"],["dc.date.available","2018-11-07T11:15:34Z"],["dc.date.issued","2008"],["dc.description.abstract","A novel carbamate prodrug 2 containing a pentagastrin moiety was synthesized. 2 was designed as a detoxified analogue of the highly cytotoxic natural antibiotic duocarmycin SA (1) for the use in a targeted prodrug monotherapy of cancers expressing cholecystokinin (CCK-B)/gastrin receptors. The synthesis of prodrug 2 was performed using a palladium-catalyzed carbonylation of bromide 6, followed by a radical cyclisation to give the pharmacophoric unit 10, coupling of 10 to the DNA-binding subunit 15 and transformation of the resulting seco-drug 3b into the carbamate 2 via addition of a pentagastrin moiety."],["dc.identifier.doi","10.3390/ijms9050821"],["dc.identifier.isi","000256308000009"],["dc.identifier.pmid","19325786"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8267"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54393"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Mdpi Ag"],["dc.relation.issn","1661-6596"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Synthesis and biological evaluation of a novel pentagastrin-toxin conjugate designed for a targeted prodrug monotherapy of cancer"],["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"]]