OP-41 ISBOMC `10 5.7 – 9.7. 2010 <strong>Ruhr</strong>-<strong>Universität</strong> <strong>Bochum</strong> Multi-Organometallic-Containing Peptide Nucleic Acids: Preparation and Biological Applications Gilles Gasser, *a,b Antonio Pinto, b Sebastian Neuman b and Nils Metzler-Nolte *b a University <strong>of</strong> Zurich, Institute <strong>of</strong> Inorganic Chemistry, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. E-mail: gilles.gasser@aci.uzh.ch; b <strong>Ruhr</strong>-University <strong>Bochum</strong>, Faculty <strong>of</strong> Chemistry and Biochemistry, Department <strong>of</strong> Bioinorganic Chemistry, <strong>Universität</strong>strasse 150, D-44780 <strong>Bochum</strong>, Germany. Peptide nucleic acids (PNAs) are non-natural nucleic acid analogues. Their neutral pseudopeptide backbone is made <strong>of</strong> N-(2-aminoethyl)glycine units which are ligated via a methylene carbonyl to the four nucleobases (Figure 1). 1 In comparison to double-stranded DNA (dsDNA), corresponding PNA•DNA hybrids are thermally more stable due to the missing electrostatic repulsion between the strands. Moreover, PNA is much more mismatch sensitive than DNA enabling sensitive and selective mismatches discrimination. All these favourable features led to application <strong>of</strong> PNAs in various research areas such as antisense and antigene therapies or biosensing. O HO P O O O Base O O P O O O Base O O P O O n O Base OH 57 HO O O N Base N H O O DNA PNA Figure 1. Structure comparison between DNA and PNA. N Base N H Base O O N NH2 In order to modify the intrinsic properties <strong>of</strong> PNAs or in order to add new functionalities and/or spectroscopic properties to PNA oligomers, organometallics have been synthetically attached to these non-natural DNA analogues. During this talk, we will present our recent advances on the preparation <strong>of</strong> multi-organometallic-containing PNA monomers and oligomers as well as their potential for biological purposes (see Figure 2 for an example <strong>of</strong> application <strong>of</strong> metal-containing PNAs). 2-6 Figure 2. Re-containing PNA oligomer mediated the silencing <strong>of</strong> enhanced green fluorescent protein (eGFP) in HeLa-eGFP cells 48 h after cellular delivery by electroporation. (200 x magnification in all images) References 1. P.E. Nielsen, P., M. Egholm, R.H. Berg, O. Buchardt, Science 1991, 254, 1497-1500 2. G. Gasser, N. Hüsken, S.D. Köster and N. Metzler-Nolte, Chem. Comm. 2008, 3675-3677. 3. N. Hüsken, G. Gasser, S.D. Köster and N. Metzler-Nolte, Bioconjugate Chem. 2009, 20, 1578–1586. 4. G. Gasser, O. Brosch, A. Ewers, T. Weyhermüller and N. Metzler-Nolte, Dalton Trans. 2009, 4310- 4317. 5. A. Sosniak, G. Gasser and N. Metzler-Nolte, Org. Biomol. Chem. 2009, 7, 4992 – 5000. 6. M. Patra, G. Gasser, D. Bobukhov, K. Merz, A.V. Shtemenko and N. Metzler-Nolte, 2010, submitted. n
ISBOMC `10 5.7 – 9.7. 2010 <strong>Ruhr</strong>-<strong>Universität</strong> <strong>Bochum</strong> Poster presentations 58