Book of Abstracts - Ruhr-Universität Bochum

P-17
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Organometallic Complexes Coupled to Cell-Penetrating Peptides: Generation of
Promising New Cytostatic Compounds
K. Splith, a Jan Hoyer, a Wanning Hu, b Ulrich Schatzschneider, b Yvonne Geldmacher, c
Malte Kokoschka, c William S. Sheldrick, c and Ines Neundorf *a
a Leipzig University, Faculty of Biosciences, Pharmacy and Psychology, Department of Biochemistry,
Brüderstr. 34, 04103, Leipzig, Germany. b Ruhr-University Bochum, Faculty of Chemistry and
Biochemistry, Department of Inorganic Chemistry I, Universitätsstr.150, 44801, Bochum, Germany.
c Ruhr-University Bochum, Faculty of Chemistry and Biochemistry, Department of Analytical
Chemistry, Universitätsstr.150 ,44801, Bochum, Germany. E-mail: splith@uni-leipzig.de
Bioorganometallic chemistry has become more and more important in several fields, especially in the
development of new drugs for cancer treatment. A number of metal-based building blocks have
promising features for applications in therapy and diagnosis. Introduction of a metal centre could add
new features which might help to overcome some problems in cancer treatment. However the low
water solubility and bioavailability of these organometallic compounds inhibits their therapeutic use in
medicine. Recently, so called cell-penetrating peptides (CPP) have emerged as potent tools to
introduce substances into cells. CPP are an inhomogenic group of peptides that share the ability to
translocate in a large number of different cell-lines without the need of a receptor or transporter
molecule. Thereby they are capable to transport various cargos inside cells, like proteins,
oligonucleotides, nanoparticles or small organic drugs. 1,2
This work describes the coupling of metal-based building blocks to cell-penetrating peptides based on
an antimicrobial peptide cathelicidin CAP18. 3 Synthesis was achieved by solid phase peptide synthesis
using standard Fmoc chemistry and activation by HOBt/DIC. Several different metal complexes have
been investigated, e.g. half-sandwich-complexes of different metals. Cellular uptake of the new
bioconjugates was investigated with different methods and high accumulation in different tumour cells
could be observed. Furthermore, cell viability assays showed that those organometallic peptide
conjugates are very potent and possess promising cytotoxic properties. 4,5,6
References
1. K. M. Stewart, K. L. Horton, S. O. Kelley, Org. Biomol. Chem. 2008, 6, 2242-2255.
2. I. Neundorf, R. Rennert, J. Franke, I. Közle, R. Bergmann, Bioconjugate Chem. 2008, 8, 1596-603.
3. I. Neundorf, R. Rennert, J. Hoyer, F. Schramm, K. Löbner, I. Kitanovic, S. Wölfl, Pharmaceuticals 2009, 2,
49-65.
4. I. Neundorf, J. Hoyer, K. Splith, R. Rennert, H.W. Peindy N’dongo, U. Schatzschneider, Chem. Commun.
2008, 43, 5604-5606.
5. K. Splith, I. Neundorf, W. Hu, H.W. Peindy N'dongo, V. Vasylyeva, K. Merz, U. Schatzschneider, Dalton
Trans. 2010, 39, 2536-2545.
6. K. Splith, W. Hu, U. Schatzschneider, R. Gust, I. Ott, I. Neundorf, manuscript submitted.
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