International Journal of Medical Sciences

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23 October 2017

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Int J Med Sci 2010; 7(4):213-223. doi:10.7150/ijms.7.213

Research Paper

Extension of the PNA world by functionalized PNA monomers eligible candidates for inverse Diels Alder Click Chemistry

Manfred Wiessler1, Waldemar Waldeck2, Ruediger Pipkorn3, Christian Kliem1, Peter Lorenz1, Heinz Fleischhacker1, Manuel Hafner4, Klaus Braun1

1. German Cancer Research Center, Dept. of Imaging and Radiooncology, INF 280, D-69120 Heidelberg, Germany
2. German Cancer Research Center, Division of Biophysics of Macromolecules, INF 580, D-69120 Heidelberg, Germany
3. German Cancer Research Center, Central Peptide Synthesis Unit, INF 580, D-69120 Heidelberg, Germany
4. Mannheim University of Applied Sciences, Department of Biotechnology, Paul-Wittsack-Straße 10, D-68163 Mannheim, Germany

Abstract

Progress in genome research led to new perspectives in diagnostic applications and to new promising therapies. On account of their specificity and sensitivity, nucleic acids (DNA/RNA) increasingly are in the focus of the scientific interest. While nucleic acids were a target of therapeutic interventions up to now, they could serve as excellent tools in the future, being highly sequence-specific in molecular diagnostics. Examples for imaging modalities are the representation of metabolic processes (Molecular Imaging) and customized therapeutic approaches (“Targeted Therapy”). In the individualized medicine nucleic acids could play a key role; this requires new properties of the nucleic acids, such as stability. Due to evolutionary reasons natural nucleic acids are substrates for nucleases and therefore suitable only to a limited extent as a drug. To use DNA as an excellent drug, modifications are required leading e.g. to a peptide nucleic acid (PNA). Here we show that an easy substitution of nucleobases by functional molecules with different reactivity like the Reppe anhydride and pentenoic acid derivatives is feasible. These derivatives allow an independent multi-ligation of functionalized compounds, e.g. pharmacologically active ones together with imaging components, leading to local concentrations sufficient for therapy and diagnostics at the same time. The high chemical stability and ease of synthesis could enhance nucleic chemistry applications and qualify PNA as a favourite for delivery. This system is not restricted to medicament material, but appropriate for the development of new and highly efficient drugs for a sustainable pharmacy.

Keywords: Click Chemistry, Diels Alder Reactioninvers (DARinv), Peptide Nucleic Acid (PNA), PNA building block functionalization

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How to cite this article:
Wiessler M, Waldeck W, Pipkorn R, Kliem C, Lorenz P, Fleischhacker H, Hafner M, Braun K. Extension of the PNA world by functionalized PNA monomers eligible candidates for inverse Diels Alder Click Chemistry. Int J Med Sci 2010; 7(4):213-223. doi:10.7150/ijms.7.213. Available from http://www.medsci.org/v07p0213.htm