Tietze, Lutz Friedjan

[["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","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","304"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Anti-Cancer Agents in Medicinal Chemistry"],["dc.bibliographiccitation.lastpage","325"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Krewer, Birgit"],["dc.date.accessioned","2018-11-07T08:31:50Z"],["dc.date.available","2018-11-07T08:31:50Z"],["dc.date.issued","2009"],["dc.description.abstract","In recent years, a series of new and highly cytotoxic analogues of CC-1065 and the duocarmycins have been developed that can be transformed into much less toxic prodrugs for the use in antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) and prodrug monotherapy (PMT) of cancer. In all these approaches, a relatively non-toxic prodrug is applied and subsequently converted selectively in the tumour tissue into a highly cytotoxic drug, thus reducing undesired side effects accompanying conventional chemotherapy. Here, the design and biological evaluation of prodrugs based on analogues of CC-1065 and the duocarmycins for the use in tumour selective cancer therapies is reviewed. The advantage of this approach is the excellent therapeutic index of some of the new prodrugs of over 5000 and the high cytotoxicity of the corresponding drugs with IC(50) values of as low as 16 pM (IC(50): concentration required for 50 % growth inhibition of target cells). In addition, a novel method for the correlation of the alkylation efficiency and the cytotoxicity based on mass spectrometry is described."],["dc.identifier.isi","000265079900004"],["dc.identifier.pmid","19275523"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17206"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bentham Science Publ Ltd"],["dc.relation.issn","1871-5206"],["dc.title","Novel Analogues of CC-1065 and the Duocarmycins for the Use in Targeted Tumour Therapies"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","205"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Chemical Biology & Drug Design"],["dc.bibliographiccitation.lastpage","211"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","Krewer, Birgit"],["dc.date.accessioned","2018-11-07T11:24:36Z"],["dc.date.available","2018-11-07T11:24:36Z"],["dc.date.issued","2009"],["dc.description.abstract","The antibody-directed enzyme prodrug therapy allows a selective liberation of cytotoxic agents from non-toxic prodrugs in cancerous tissue by targeted antibody-enzyme conjugates. We have developed a series of novel glycosidic prodrugs based on the natural antibiotic CC-1065 and the duocarmycins, which are up to 4800 times less toxic than the drugs liberated from these prodrugs in the presence of the activating enzyme (e.g., beta-d-galactosidase). Furthermore, the drugs show very high cytotoxicities with IC(50) values of as low as 4.5 pm. In this report, we summarize our recent results on the development and biological evaluation of these novel third-generation prodrugs with higher water solubility, higher difference in cytotoxicity between the prodrugs and the corresponding drugs and improved cytotoxicity of the drugs as compared with previous compounds."],["dc.identifier.doi","10.1111/j.1747-0285.2009.00856.x"],["dc.identifier.isi","000269058200001"],["dc.identifier.pmid","19660031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56442"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","1747-0277"],["dc.title","Antibody-Directed Enzyme Prodrug Therapy: A Promising Approach for a Selective Treatment of Cancer Based on Prodrugs and Monoclonal Antibodies"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1946"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","ChemMedChem"],["dc.bibliographiccitation.lastpage","1955"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Tietze, Lutz Friedjan"],["dc.contributor.author","von Hof, J. Marian"],["dc.contributor.author","Krewer, Birgit"],["dc.contributor.author","Mueller, Michael"],["dc.contributor.author","Major, Felix"],["dc.contributor.author","Schuster, Heiko J."],["dc.contributor.author","Schuberth, Ingrid"],["dc.contributor.author","Alves, Frauke"],["dc.date.accessioned","2018-11-07T11:08:25Z"],["dc.date.available","2018-11-07T11:08:25Z"],["dc.date.issued","2008"],["dc.description.abstract","A severe limitation in cancer therapy is the often insufficient differentiation between malign and benign tissue using known chemotherapeutics. One approach to decrease side effects is antibody-directed enzyme prodrug therapy (ADEPT). We have developed new glycosidic prodrugs such as (-)-(1S)-26b based on the antibiotic (+)-duocarmycin SA ((+)-1) with a QIC(50) value of 3500 (QIC(50)=IC(50) of prodrug/IC(50) of prodrug+enzyme) and an IC(50) value for the corresponding drug (prodrug + enzyme) of 16pM. The asymmetric synthesis of the precursor (-)-(1S)-19 was performed by arylation of the enantiomerically pure epoxide (+)-(S)29 (>= 98% ee)."],["dc.identifier.doi","10.1002/cmdc.200800250"],["dc.identifier.isi","000261877100015"],["dc.identifier.pmid","19021160"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52775"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1860-7179"],["dc.title","Asymmetric Synthesis and Biological Evaluation of Glycosidic Prodrugs for a Selective Cancer Therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]