ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
O17. Synthesis And Dna Binding Studies Of End-Functionalised Metallo-
Supramolecular Cylinders
L. Cardo and M.J. Hannon
School of Chemistry, University of Birmingham, B15 2LH, Birmingham, United Kingdom
e-mail: lxc577@bham.ac.uc
The design and development of new metallo-based drugs, capable of interacting and selectively recognising the
DNA, is a major challenge in the field of bioinorganic chemistry. We recently reported that di- and tetra-cationic
supramolecular “cylinders” not only are able to bind in the major groove of natural polymeric DNA [1] and at
the heart of DNA 3-way junctions [2], but they also exhibit a remarkable cytotoxic activity against cancer cell
lines [3].
These results motivated us to examine useful modifications of these complexes, particularly to explore whether
DNA recognition motifs [4], such as amino acids or short peptides, might be attached to the cylinders to provide
a route to targeting the cylinder activity to particular genes on the DNA. Furthermore, mono- and di-capping of
the cylinders are both being investigated (Figure 1).
Herein, we report a versatile procedure to end-functionalise the cylinders by amido bonds. This allow us to
obtain our first hybrids [5]: one di-Fe(II) triple-stranded, two di-Cu(I) and one di-Ag(I) double-stranded
cylinders have been conjugated to Gly-Gly-Ser peptide sequences; a di-Fe(II) triple stranded complex has also
been fuctionalised with arginine residues and a very interesting effect on the chirality of the resulting helicate has
been observed. DNA-binding and cleavage studies confirm that the end-functionalisation does not prevent the
inherent cylinder DNA recognition properties from being expressed.
Figure 1: Representation of designed end-functionalised triple stranded cylinder.
Acknowledgement: University of Birmingham for funding.
References:
[1] M.J. Hannon, V. Moreno, M.J. Prieto, E. Molderheim, E. Sletten, I. Meistermann, C.J. Isaac, K.J. Sanders
and A. Rodger, Angew. Chem., Intl. Ed., 40, 879 (2001); I. Meistermann, V. Moreno, M.J. Prieto, E.
Moldrheim, E. Sletten, S. Khalid, P. M. Rodger, J.C. Peberdy, C.J. Isaac, A. Rodger and M.J. Hannon, Proc.
Natl. Acad. Sci., 99, 5069 (2002); C. Uerpmann, J. Malina, M. Pascu, G.J. Clarkson, V. Moreno, A. Rodger, A.
Grandas and M.J. Hannon, Chem. Eur. J. 11, 1750 (2005).
[2] A. Oleksy, A.G. Blanco, R. Boer, I. Usón, J. Aymami, A. Rodger, M.J. Hannon and M. Coll, Angew. Chem.,
Intl. Ed., 45 1227 (2005).
[3] A.C.G. Hotze, B.M. Kariuki, M.J. Hannon, Angew. Chem., Int. Ed. 45, 4839 (2006); G.I. Pascu, A.C.G.
Hotze, C. Sanchez Cano, B.M. Kariuki, M.J. Hannon, Angew. Chem., Int. Ed. 46, 4374 (2007).
[4] S. Neidle, Nucleic acid structure and recognition, Oxford University Press. Oxford (2002).
[5] L. Cardo, M.J. Hannon, Inorg. Chim. Acta (2008), special issue, doi:10.1016/j.ica.2008.02.050, in press.
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