Peptide nucleic acid chimerae

Borgatti M., Lampronti 1., Romanelli A., Pedone C., Saviano M., Bianchi N., Mischiati C, Gambari R. Transcription factor decoy molecules based on a peptide nucleic acid (PNA)-DNA chimera mimicking Spl binding sites./. Biol. Chem. 2003 278 7500-7509. 

Peptide nucleic acid (PNA) has received considerable attention for several years as a candidate for antisense exploitation. Several publications have addressed the physical and biological properties, applications and characterisation of PNA and modified PNAs. One problem associated with PNA is its poor solubility. There has therefore been interest in the synthesis of mixed PNA-DNA chimeras " and the introduction of charge into the PNA monomer itself. Phosphonate PNA 157a has been prepared using the aminomethylpho-sphonate 157b. Proline derived PNA monomers 158 have been described. ... 

Since Nielsen et al introduced peptide nucleic acids (PNA), this area has received vast attention, and continues to do so. More recently, the main area of interest has been in novel analogues, and many new ones have been reported. The solid phase synthesis of DNA-3 -PNA chimeras have been described, in which the DNA is attached to the amino terminal of the PNA via the 3 -phosphate or thiophosphate. All chimeras were shown to have superior thermal stability towards either DNA or RNA than a DNA oligomer, and the phosphodiester linkage was more stable than the phosphorothioate. Hybridisation studies with PNA and PNA-DNA chimeras demonstrate that there is a sequence effect for the junction between PNA and DNA on duplex stability. A decamer pyrimidine bis-PNA oligomer, separated by a linker, when targeted to complementary dsDNA formed three distinct structures. One structure contained two bis-PNA units, and the other two were believed to be structural isomers. 

Peptide nucleic acid (PNA) was introduced by Nielsen and coworkers, and is a chimera of DNA nucleobases with a peptide backbone (see also section 3.1 on ohgonucleotide-peptide conjugates). PNA is based on an aminoethyl-glycine backbone (18), and is therefore neutral. PNA binds tightly to complementary nucleic add, and is resistant to nucleases. One drawback of PNA is that sequences are often insoluble, and one way to resolve this is to include a lysine taU onto the PNA. Reports on PNA during this review period include new synthetic approaches, a number of new analogues as well as many novel apphcations. 

Uhlmann, E. (1998). Peptide nucleic acids (PNA) and PNA-DNA chimeras From high binding affinity towards biological function, Biol Chem. 379,1045-1052. 

Zhang X., Ishihara T, Corey D. R. Strand invasion by mixed base PNAs and a PNA-peptide chimera. Nucleic Acids Res. 2000 28 3332-3338. 

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