Publikation:

Modification of daunorubicin-GnRH-III bioconjugates with oligoethylene glycol derivatives to improve solubility and bioavailability for targeted cancer chemotherapy

Lade...
Vorschaubild

Dateien

Zu diesem Dokument gibt es keine Dateien.

Datum

2015

Autor:innen

Hegedüs, Rózsa
Pauschert, Aline
Orbán, Erika
Szabó, Ildikó
Andreu, David
Mező, Gábor

Herausgeber:innen

Kontakt

ISSN der Zeitschrift

Electronic ISSN

ISBN

Bibliografische Daten

Verlag

Schriftenreihe

Auflagebezeichnung

URI (zitierfähiger Link)
DOI (zitierfähiger Link)
ArXiv-ID

Internationale Patentnummer

Angaben zur Forschungsförderung

Projekt

Open Access-Veröffentlichung
Core Facility der Universität Konstanz

Gesperrt bis

Titel in einer weiteren Sprache

Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published

Erschienen in

Peptide Science. 2015, 104(3), pp. 167-177. ISSN 0006-3525. eISSN 1097-0282. Available under: doi: 10.1002/bip.22629

Zusammenfassung

Daunorubicin-GnRH-III bioconjugates have recently been developed as drug delivery systems with potential applications in targeted cancer chemotherapy. In order to improve their biochemical properties, several strategies have been pursued: (1) incorporation of an enzymatic cleavable spacer between the anticancer drug and the peptide-based targeting moiety, (2) peptide modification by short chain fatty acids or (3) attachment of two anticancer drugs to the same GnRH-III derivative. Although these modifications led to more potent bioconjugates, a decrease in their solubility was observed. Here we report on the design, synthesis and biochemical characterization of daunorubicin-GnRH-III bioconjugates with increased solubility, which could be achieved by incorporating oligoethylene glycol-based spacers in their structure. First, we have evaluated the effect of an oligoethylene glycol-based spacer on the solubility, enzymatic stability/degradation, cellular uptake and in vitro cytostatic effect of a bioconjugate containing only one daunorubicin attached through a GFLG tetrapeptide spacer to the GnRH-III targeting moiety. Thereafter, more complex compounds containing two copies of daunorubicin, GFLG spacers as well as Lys(nBu) in position 4 of GnRH-III were synthesized and biochemically characterized. Our results indicated that all synthesized oligoethylene glycol-containing bioconjugates had higher solubility in cell culture medium than the unmodified analogs. They were degraded in the presence of rat liver lysosomal homogenate leading to the formation of small drug containing metabolites. In the case of bioconjugates containing two copies of daunorubicin, the incorporation of oligoethylene glycol-based spacers led to increased in vitro cytostatic effect on MCF-7 human breast cancer cells.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
540 Chemie

Schlagwörter

Konferenz

Rezension
undefined / . - undefined, undefined

Forschungsvorhaben

Organisationseinheiten

Zeitschriftenheft

Zugehörige Datensätze in KOPS

Zitieren

ISO 690HEGEDÜS, Rózsa, Aline PAUSCHERT, Erika ORBÁN, Ildikó SZABÓ, David ANDREU, Andreas MARQUARDT, Gábor MEZŐ, Marilena MANEA, 2015. Modification of daunorubicin-GnRH-III bioconjugates with oligoethylene glycol derivatives to improve solubility and bioavailability for targeted cancer chemotherapy. In: Peptide Science. 2015, 104(3), pp. 167-177. ISSN 0006-3525. eISSN 1097-0282. Available under: doi: 10.1002/bip.22629
BibTex
@article{Hegedus2015Modif-31099,
  year={2015},
  doi={10.1002/bip.22629},
  title={Modification of daunorubicin-GnRH-III bioconjugates with oligoethylene glycol derivatives to improve solubility and bioavailability for targeted cancer chemotherapy},
  url={http://onlinelibrary.wiley.com/doi/10.1002/bip.22629/abstract},
  number={3},
  volume={104},
  issn={0006-3525},
  journal={Peptide Science},
  pages={167--177},
  author={Hegedüs, Rózsa and Pauschert, Aline and Orbán, Erika and Szabó, Ildikó and Andreu, David and Marquardt, Andreas and Mező, Gábor and Manea, Marilena}
}
RDF
<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/server/rdf/resource/123456789/31099">
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52"/>
    <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/31099"/>
    <dc:creator>Orbán, Erika</dc:creator>
    <dc:creator>Manea, Marilena</dc:creator>
    <dc:creator>Pauschert, Aline</dc:creator>
    <dc:contributor>Manea, Marilena</dc:contributor>
    <dc:contributor>Orbán, Erika</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-06-02T13:13:59Z</dcterms:available>
    <dcterms:title>Modification of daunorubicin-GnRH-III bioconjugates with oligoethylene glycol derivatives to improve solubility and bioavailability for targeted cancer chemotherapy</dcterms:title>
    <dc:contributor>Pauschert, Aline</dc:contributor>
    <dc:creator>Andreu, David</dc:creator>
    <dc:contributor>Szabó, Ildikó</dc:contributor>
    <dc:contributor>Marquardt, Andreas</dc:contributor>
    <dc:creator>Hegedüs, Rózsa</dc:creator>
    <dc:creator>Szabó, Ildikó</dc:creator>
    <dc:creator>Marquardt, Andreas</dc:creator>
    <dcterms:abstract xml:lang="eng">Daunorubicin-GnRH-III bioconjugates have recently been developed as drug delivery systems with potential applications in targeted cancer chemotherapy. In order to improve their biochemical properties, several strategies have been pursued: (1) incorporation of an enzymatic cleavable spacer between the anticancer drug and the peptide-based targeting moiety, (2) peptide modification by short chain fatty acids or (3) attachment of two anticancer drugs to the same GnRH-III derivative. Although these modifications led to more potent bioconjugates, a decrease in their solubility was observed. Here we report on the design, synthesis and biochemical characterization of daunorubicin-GnRH-III bioconjugates with increased solubility, which could be achieved by incorporating oligoethylene glycol-based spacers in their structure. First, we have evaluated the effect of an oligoethylene glycol-based spacer on the solubility, enzymatic stability/degradation, cellular uptake and in vitro cytostatic effect of a bioconjugate containing only one daunorubicin attached through a GFLG tetrapeptide spacer to the GnRH-III targeting moiety. Thereafter, more complex compounds containing two copies of daunorubicin, GFLG spacers as well as Lys(nBu) in position 4 of GnRH-III were synthesized and biochemically characterized. Our results indicated that all synthesized oligoethylene glycol-containing bioconjugates had higher solubility in cell culture medium than the unmodified analogs. They were degraded in the presence of rat liver lysosomal homogenate leading to the formation of small drug containing metabolites. In the case of bioconjugates containing two copies of daunorubicin, the incorporation of oligoethylene glycol-based spacers led to increased in vitro cytostatic effect on MCF-7 human breast cancer cells.</dcterms:abstract>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Andreu, David</dc:contributor>
    <dc:contributor>Mező, Gábor</dc:contributor>
    <dc:creator>Mező, Gábor</dc:creator>
    <dc:contributor>Hegedüs, Rózsa</dc:contributor>
    <dc:language>eng</dc:language>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52"/>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2015-06-02T13:13:59Z</dc:date>
    <dcterms:issued>2015</dcterms:issued>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/29"/>
  </rdf:Description>
</rdf:RDF>

Interner Vermerk

xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter

Kontakt

Prüfdatum der URL

2015-06-02

Prüfungsdatum der Dissertation

Finanzierungsart

Kommentar zur Publikation

Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Diese Publikation teilen