Objective
Peptide nucleic acid (PNA), a conceptual DNA analog albeit of different chemical and physical structure, has been explored intensively since its presentation in 1991. A significant potential of PNA for use in "artificial restriction enzyme" strategies in genome mapping, as a probe for exploring DNA structure and its interaction with various ligands as well the use in antisense and antigene strategies has been demonstrated.
In order to extend the range of recognition sequences in double stranded DNA as well as the efficiency and selectivity in targeting mRNA, it is proposed to develop methods for synthesis PNA, with novel modified nucleobases and backbones.
The proposed work consists of two major parts. One is devoted to the synthesis of various PNA oligomers with several modifications in heterocyclic bases and aminoethylglycine backbone and will be performed in the laboratories in Moscow and Copenhagen. Another part deals with biochemical and biophysical studies of newly synthesized PNAs in terms of their specific and selective interaction with RNA and dsDNA.
This part will be performed in the laboratories in Copenhagen, Gothenburg and Moscow using;
(i) spectroscopic (circular and linear dichroism), thermal denaturation and calometry techniques,
(ii) gel electrophoresis as well as
(iii) microscopic techniques. The latter includes electron and atomic force microscopies.
It is anticipated that studying PNAs with specific base and backbone modifications will also further enable us to understand which forces govern the formation of stable complexes.
It is expected that solving the problem of recognition of non-homopurine sequences in duplex DNA will be paramount for development of efficient PNA-based antigene drugs and biomolecular tools.
Furthermore, PNAs containing modified backbones may significantly aid the development of PNA based pharmaceutical drugs, mainly addressing the issues of cellular uptake and pharmacokinetics.
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Programme(s)
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Coordinator
2200N Copenhagen
Denmark
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