Issue 10, 2012
From the journal:

Dalton Transactions

Solid-phase synthesis of oxaliplatin–TATpeptide bioconjugates

Sergey Abramkin,a   Seied M. Valiahdi,a   Michael A. Jakupec,a   Mathea S. Galanski,*a   Nils Metzler-Nolteb  and  Bernhard K. Keppler*a  

* Corresponding authors

a Institute of Inorganic Chemistry, University of Vienna, Strasse 42, Währinger, Austria
E-mail: mathea.galanski@univie.ac.at
Fax: +43 1 427752680

b Lehrstuhl für Anorganische Chemie I – Bioanorganische Chemie, Fakultät für Chemie und Biochemie, Ruhr-Universität Bochum, Universitätsstrasse 150, Germany

Abstract

Platinum-based drugs play a crucial role in the fight against cancer. Oxaliplatin, which is used in the treatment of colorectal carcinoma, was the last platinum-based agent to be approved worldwide. However, the efficiency of the therapy is limited for example by a low accumulation of the drug in cancer cells. Cell-penetrating peptides (CPPs) are known to ease the cellular membranetransport and are used as vectors for low-molecular-weight drugs and drug carriers; of them, TATpeptides are the best-studied group. In this work, a TAT-peptide fragment (YGRKKRRQRRR) was for the first time conjugated to a platinum(IV) analog of oxaliplatin as a vehicle for membrane penetration. Solid-phase peptide synthesis and subsequent coupling with the platinum complex afforded mono- and difunctionalized conjugates, which were separated by preparative HPLC and characterized by analytical HPLC, ESI-MS, and 1H NMR spectroscopy. Both conjugates are active in the low micromolar range in CH1 and SW480 human cancer cells, requiring much lower concentrations than the untargeted analogs for equal effects.

Graphical abstract: Solid-phase synthesis of oxaliplatin–TAT peptide bioconjugates

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Article information

DOI
https://doi.org/10.1039/C2DT12024K
Article type
Paper
Submitted
25 Oct 2011
Accepted
06 Dec 2011
First published
27 Jan 2012

Dalton Trans., 2012,41, 3001-3005

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Solid-phase synthesis of oxaliplatin–TATpeptide bioconjugates

S. Abramkin, S. M. Valiahdi, M. A. Jakupec, M. S. Galanski, N. Metzler-Nolte and B. K. Keppler, Dalton Trans., 2012, 41, 3001 DOI: 10.1039/C2DT12024K

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