Peptide Nucleic Acids, Morpholinos and Related Antisense Biomolecules
This volume is unique to the existing literature in the Peptide Nucleic Acid field, in that it focuses on comparing and contrasting PNA with other available oligonucleotide homologues and considers areas in which these biomolecules could be profitably app
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The Many Faces of PNA Peter E. Nielsen Introduction to PNA
P
eptide nucleic acids or PNA (Fig. 1) were originally conceived as mimics of triple helix forming oligonucleotides designed for sequence specific targeting of double stranded DNA via major groove recognition. It very quickly became clear that PNA is indeed a very potent structural mimic of DNA, capable of forming Watson-crick base pair dependent double helices with sequence complementary DNA, RNA or PNA."^' It also turned out that triplexes formed between two homopyrimidine PNA strands and a complementary homopurine DNA (or RNA) target are exceptionally stable and that "triplex targeting" of double stranded DNA results in a strand displacement complex involving an internal PNA2-DNA triplex rather than a "traditional" PNA-DNA2 triplex. These basic hybridization and structural properties combined with the simple and robust chemistry of the amino-ethyl-glycine-PNA, or aeg-PNA, has attracted attention from many areas of science, including bioorganic chemistry, drug development, molecular biology, genetic diagnostics, prebiotic evolution, and emergingly also materials science. Much of the development during the past ten years has been continuously reviewed over the years and many recent reviews have focused on specialized aspects of PNA applications and chemistry (viz. 5-12). In the present chapter, it is my goal to present an overview of this development stressing highlights, major break-throughs, and the most recent progress as well as future prospects.
PNA Chemistry The PNA structure consists of three parts (Fig. 1). The backbone is composed of a glycine with an aminoethyl extension from the amine, thereby providing the correct internucleobase spacing, and the nucleobases are attached to the "glycine nitrogen" via an amide linkage as acetic acid derivatives. Thus PNA monomers are amino acids that can be oligomertized by conventional solid phase peptide chemistry using, e.g., Boc- or Fmoc-protection strategy. Furthermore, the synthesis of PNA monomers (especially Boc-protected) is straightforward and allows access to a variety of nonnatural nucleobases.^ '^^ The simplicity of the PNA strucmre has inspired many chemists to explore other amide-based DNA mimics."^^ Because the PNA backbone structure has more degrees of freedom than DNA, it should also be possible to obtain derivatives that bind even tighter to DNA and RNA by conformationally constraining the backbone, most obviously by introducing cyclic structures in the backbone. A large variety of these have been prepared, but only one seems to hold some promise, the aminoethyl proline or aep-PNA. It is, however, too early to judge the potential of this aepPNA because the hybridization properties appear to be very context-dependent in a way that has not been fiiUy elucidated.^^
Peptide Nucleic Acids, Morpholinos and Related Antisense Biomolecules^ edited by C.G. Janson and M.J. During. ©2006 Eurekah.com and Kluwer Academic / Plenum Publishers.
Peptide Nucleic Acids, Morpholinos and Related Antisense Bio
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