The crystal structure of non-modified and bipyridine-modified PNA duplexes.

Joanne I Yeh,Ehmke Pohl,Wei He,George M Sheldrick,Shoucheng Du,Daphne Truan,Catalina Achim

doi:10.1002/chem.201000392

Abstract

Peptide nucleic acid (PNA) is a synthetic analogue of DNA that commonly has an N-aminoethyl glycine backbone. The crystal structures of two PNA duplexes, one containing eight standard nucleobase pairs (GGCATGCC)(2), and the other containing the same nucleobase pairs and a central pair of bipyridine ligands, have been solved with a resolution of 1.22 and 1.10 Å, respectively. The non-modified PNA duplex adopts a P-type helical structure similar to that of previously characterized PNAs. The atomic-level resolution of the structures allowed us to observe for the first time specific modes of interaction between the terminal lysines of the PNA and the backbone and the nucleobases situated in the vicinity of the lysines, which are considered an important factor in the induction of a preferred handedness in PNA duplexes. Our results support the notion that whereas PNA typically adopts a P-type helical structure, its flexibility is relatively high. For example, the base-pair rise in the bipyridine-containing PNA is the largest measured to date in a PNA homoduplex. The two bipyridines bulge out of the duplex and are aligned parallel to the major groove of the PNA. In addition, two bipyridines from adjacent PNA duplexes form a π-stacked pair that relates the duplexes within the crystal. The bulging out of the bipyridines causes bending of the PNA duplex, which is in contrast to the structure previously reported for biphenyl-modified DNA duplexes in solution, where the biphenyls are π stacked with adjacent nucleobase pairs and adopt an intrahelical geometry. This difference shows that relatively small perturbations can significantly impact the relative position of nucleobase analogues in nucleic acid duplexes.

Highlights

Peptide nucleic acid (PNA) is a synthetic analogue of DNA that has a pseudo-peptide backbone instead of the sugar diphosphate backbone of the DNA (Figure 1).[1,2,3] PNA forms homoduplexes by Watson Crick hybridization
The only disordered region is at the C-terminal lysines of the 8-bp PNA, which cannot be traced beyond the Cβ position in any of the four strands
The crystal structure of non-modified and bipyridine-modified PNAs reported in this paper have the highest resolution reported to date for a PNA crystal structure

Summary

Introduction

Peptide nucleic acid (PNA) is a synthetic analogue of DNA that has a pseudo-peptide backbone instead of the sugar diphosphate backbone of the DNA (Figure 1).[1,2,3] PNA forms homoduplexes by Watson Crick hybridization. Numerous DNA and PNA duplexes incorporating one or multiple metal complexes have been studied in the last decade.[7,8,9,10,11] In most of these studies, the ligands incorporated in the nucleic acid duplex were aromatic and the metal complexes were square planar to (1) make possible π stacking between the complex and adjacent base pairs, and (2) minimize structural distortions of the duplex. While the thermal stability of the ligand- and metal-containing nucleic acids has been routinely studied, structural information about the duplexes before and after the incorporation of ligands and metal ions has been obtained only in a few cases. Such information is important for the rational design of metal-containing PNA nanostructures

Results

Discussion

Conclusion