Solid-phase synthesis of oxaliplatin-TAT peptide bioconjugates
- Author(s)
- Sergey Abramkin, Seied Mojtaba Valiahdi, Michael Jakupec, Mathea Sophia Galanski, Nils Metzler-Nolte, Bernhard Keppler
- 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 membrane transport and are used as vectors for low-molecular-weight drugs and drug carriers; of them, TAT peptides 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 H-1 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.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Ruhr-Universität Bochum (RUB)
- Journal
- Dalton Transactions
- Volume
- 41
- Pages
- 3001-3005
- No. of pages
- 5
- ISSN
- 1477-9226
- DOI
- https://doi.org/10.1039/c2dt12024k
- Publication date
- 2012
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 302055 Oncology, 301305 Medical chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/bfabd49e-83c3-46c2-a483-f68c5810f1d9