KOPS - Das Institutionelle Repositorium der Universität Konstanz

In vitro degradation and antitumor activity of oxime bond-linked daunorubicin–GnRH-III bioconjugates and DNA-binding properties of daunorubicin–amino acid metabolites

In vitro degradation and antitumor activity of oxime bond-linked daunorubicin–GnRH-III bioconjugates and DNA-binding properties of daunorubicin–amino acid metabolites

Zitieren

Dateien zu dieser Ressource

Prüfsumme: MD5:e9e7f53f4bd7b588173ed3b68f1dc131

ORBÁN, Erika, Gábor MEZŐ, Pascal SCHLAGE, Gabriella CSÍK, Zarko KULIC, Philipp ANSORGE, Erzsébet FELLINGER, Heiko MÖLLER, Marilena MANEA, 2011. In vitro degradation and antitumor activity of oxime bond-linked daunorubicin–GnRH-III bioconjugates and DNA-binding properties of daunorubicin–amino acid metabolites. In: Amino Acids. 41(2), pp. 469-483. ISSN 0939-4451. eISSN 1438-2199. Available under: doi: 10.1007/s00726-010-0766-1

@article{Orban2011vitro-12610, title={In vitro degradation and antitumor activity of oxime bond-linked daunorubicin–GnRH-III bioconjugates and DNA-binding properties of daunorubicin–amino acid metabolites}, year={2011}, doi={10.1007/s00726-010-0766-1}, number={2}, volume={41}, issn={0939-4451}, journal={Amino Acids}, pages={469--483}, author={Orbán, Erika and Mező, Gábor and Schlage, Pascal and Csík, Gabriella and Kulic, Zarko and Ansorge, Philipp and Fellinger, Erzsébet and Möller, Heiko and Manea, Marilena} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/12610"> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dc:language>eng</dc:language> <dc:creator>Kulic, Zarko</dc:creator> <dc:creator>Orbán, Erika</dc:creator> <dc:contributor>Ansorge, Philipp</dc:contributor> <dcterms:title>In vitro degradation and antitumor activity of oxime bond-linked daunorubicin–GnRH-III bioconjugates and DNA-binding properties of daunorubicin–amino acid metabolites</dcterms:title> <dc:contributor>Fellinger, Erzsébet</dc:contributor> <dc:rights>deposit-license</dc:rights> <dc:contributor>Schlage, Pascal</dc:contributor> <dcterms:issued>2011</dcterms:issued> <dc:creator>Fellinger, Erzsébet</dc:creator> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/52"/> <dc:contributor>Mező, Gábor</dc:contributor> <dcterms:bibliographicCitation>First publ. in: Amino Acids 41 (2011), 2, pp. 469-483, DOI: 10.1007/s00726-010-0766-1</dcterms:bibliographicCitation> <dc:creator>Mező, Gábor</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2012-07-31T22:25:05Z</dcterms:available> <dc:contributor>Orbán, Erika</dc:contributor> <dc:creator>Ansorge, Philipp</dc:creator> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dc:creator>Manea, Marilena</dc:creator> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-06-09T07:43:11Z</dc:date> <dc:contributor>Manea, Marilena</dc:contributor> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103605204-4002607-1"/> <dcterms:abstract xml:lang="eng">Bioconjugates with receptor-mediated tumor-targeting functions and carrying cytotoxic agents should enable the specific delivery of chemotherapeutics to malignant tissues, thus increasing their local efficacy while limiting the peripheral toxicity. In the present study, gonadotropin-releasing hormone III (GnRH-III; Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was employed as a targeting moiety to which daunorubicin was attached via oxime bond, either directly or by insertion of a GFLG or YRRL tetrapeptide spacer. The in vitro antitumor activity of the bioconjugates was determined on MCF-7 human breast and HT-29 human colon cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Their degradation/stability (1) in human serum, (2) in the presence of cathepsin B and (3) in rat liver lysosomal homogenate was analyzed by liquid chromatography in combination with mass spectrometry. The results show that (1) all synthesized bioconjugates have in vitro antitumor effect, (2) they are stable in human serum at least for 24 h, except for the compound containing an YRRL spacer and (3) they are hydrolyzed by cathepsin B and in the lysosomal homogenate. To investigate the relationship between the in vitro antitumor activity and the structure of the bioconjugates, the smallest metabolites produced in the lysosomal homogenate were synthesized and their binding to DNA was assessed by fluorescence spectroscopy. Our data indicate that the incorporation of a peptide spacer in the structure of oxime bond-linked daunorubicin–GnRH-III bioconjugates is not required for their antitumor activity. Moreover, the antitumor activity is influenced by the structure of the metabolites (daunorubicin–amino acid derivatives) and their DNA-binding properties.</dcterms:abstract> <dc:creator>Csík, Gabriella</dc:creator> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/12610"/> <dc:creator>Möller, Heiko</dc:creator> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/12610/1/Manea_Amino%20Acids.pdf"/> <dc:contributor>Kulic, Zarko</dc:contributor> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/52"/> <dc:creator>Schlage, Pascal</dc:creator> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/12610/1/Manea_Amino%20Acids.pdf"/> <dc:contributor>Möller, Heiko</dc:contributor> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> <dc:contributor>Csík, Gabriella</dc:contributor> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/29"/> </rdf:Description> </rdf:RDF>

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

Manea_Amino Acids.pdf 440

Das Dokument erscheint in:

KOPS Suche


Stöbern

Mein Benutzerkonto