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","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","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"]]