Complexes of Peptide Nucleic Acids (PNAs)

PNA (peptide nucleic acid) is an oligonucleotide analogue in which the entire backbone has been replaced by a backbone composed of N-(2-aminoethyl)glycine units [1]. PNA hybridises with both DNA and RNA and possesses many of the properties desired of an antisense/antigene drug candidate, including stability towards nucleases, proteases, peptidases and human serum. The aim of the structure determinations is to investigate how the helical form is dependent on the backbone and the nucleobases and how increased hydrogen bonding properties of PNA can be obtained. The structure of a hexameric PNA-PNA duplex has been determined to 1.7 Å resolution, revealing a unique helix (P-form) among the known Watson-Crick base-paired helices [2]. The structure was solved using a 5-bromo-uracil derivative and SR data to 1.9 Å resolution (X31). In addition, a PNA analogue with modifications in the backbone (N-methyl backbone) has been determined to 2.2 Å resolution [3]. A data set to 1.8 Å resolution (X31) has been collected on a hexameric PNA analogue with modifications in one of the nucleobases (thymine), bT-PNA, and the structure has been solved using MR. The modified base is easily accommodated in the P-form helix structure and has the Watson-Crick hydrogen bonding pattern proposed for this base [4]. Figure 1: PNA-PNA dodecamer: left-handed double helix (top, dark grey) and right-handed double heli