EGFR-targeting peptide-coupled platinum(IV) complexes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-06

AUTHORS

Josef Mayr, Sonja Hager, Bettina Koblmüller, Matthias H. M. Klose, Katharina Holste, Britta Fischer, Karla Pelivan, Walter Berger, Petra Heffeter, Christian R. Kowol, Bernhard K. Keppler

ABSTRACT

The high mortality rate of lung cancer patients and the frequent occurrence of side effects during cancer therapy demonstrate the need for more selective and targeted drugs. An important and well-established target for lung cancer treatment is the occasionally mutated epidermal growth factor receptor (EGFR). As platinum(II) drugs are still the most important therapeutics against lung cancer, we synthesized in this study the first platinum(IV) complexes coupled to the EGFR-targeting peptide LARLLT (and the shuffled RTALLL as reference). Notably, HPLC-MS measurements revealed two different peaks with the same molecular mass, which turned out to be a transcyclization reaction in the linker between maleimide and the coupled cysteine moiety. With regard to the EGFR specificity, subsequent biological investigations (3-day viability, 14-day clonogenic assays and platinum uptake) on four different cell lines with different verified EGFR expression levels were performed. Unexpectedly, the results showed neither an enhanced activity nor an EGFR expression-dependent uptake of our new compounds. Consequently, fluorophore-coupled peptides were synthesized to re-evaluate the targeting ability of LARLLT itself. However, also with these molecules, flow cytometry measurements showed no correlation of drug uptake with the EGFR expression levels. Taken together, we successfully synthesized the first platinum(IV) complexes coupled to an EGFR-targeting peptide; however, the biological investigations revealed that LARLLT is not an appropriate peptide for enhancing the specific uptake of small-molecule drugs into EGFR-overexpressing cancer cells. More... »

PAGES

591-603

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00775-017-1450-7

DOI

http://dx.doi.org/10.1007/s00775-017-1450-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084774177

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28405842


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Download the RDF metadata as:  json-ld nt turtle xml License info

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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