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dc.contributor.author
Gaugaz, Fabienne Zdenka
dc.contributor.author
Chicca, Andrea
dc.contributor.author
Redondo-Horcajo, Mariano
dc.contributor.author
Barasoain, Isabel
dc.contributor.author
Díaz, J. Fernando
dc.contributor.author
Altmann, Karl-Heinz
dc.date.accessioned
2019-03-19T10:52:07Z
dc.date.available
2019-03-16T04:12:49Z
dc.date.available
2019-03-19T10:52:07Z
dc.date.issued
2019-03-05
dc.identifier.issn
1422-0067
dc.identifier.other
10.3390/ijms20051113
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/331757
dc.identifier.doi
10.3929/ethz-b-000331757
dc.description.abstract
A new simplified, epoxide-free epothilone analog was prepared incorporating an N-(2-hydroxyethyl)-benzimidazole side chain, which binds to microtubules with high affinity and inhibits cancer cell growth in vitro with nM potency. Building on this scaffold, a disulfide-linked conjugate with the purported EGFR-binding (EGFR, epidermal growth factor receptor) peptide GE11 was then prepared. The conjugate retained significant microtubule-binding affinity, in spite of the size of the peptide attached to the benzimidazole side chain. The antiproliferative activity of the conjugate was significantly lower than for the parent scaffold and, surprisingly, was independent of the EGFR expression status of cells. Our data indicate that the disulfide-based conjugation with the GE11 peptide is not a viable approach for effective tumor-targeting of highly potent epothilones and probably not for other cytotoxics
en_US
dc.format
application/pdf
dc.language.iso
en
en_US
dc.publisher
MDPI Molecular diversity preservation international
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
cancer
en_US
dc.subject
drug discovery
en_US
dc.subject
epothilone
en_US
dc.subject
medicinal chemistry
en_US
dc.subject
microtubule-stabilizing agents
en_US
dc.subject
prodrug
en_US
dc.subject
total synthesis
en_US
dc.subject
tumor-targeting
en_US
dc.title
Synthesis, Microtubule-Binding Affinity, and Antiproliferative Activity of New Epothilone Analogs and of an EGFR-Targeted Epothilone-Peptide Conjugate
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
International Journal of Molecular Sciences
ethz.journal.volume
20
en_US
ethz.journal.issue
5
en_US
ethz.journal.abbreviated
Int. j. mol. sci.
ethz.pages.start
1113
en_US
ethz.size
19 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03647 - Altmann, Karl-Heinz / Altmann, Karl-Heinz
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03647 - Altmann, Karl-Heinz / Altmann, Karl-Heinz
ethz.date.deposited
2019-03-16T04:12:52Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2019-03-19T10:52:21Z
ethz.rosetta.lastUpdated
2022-03-28T22:34:31Z
ethz.rosetta.versionExported
true
ethz.COinS
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