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. 2003 Oct 14;100(21):12021-6.
doi: 10.1073/pnas.2034746100. Epub 2003 Sep 25.

Insights into peptide nucleic acid (PNA) structural features: the crystal structure of a D-lysine-based chiral PNA-DNA duplex

Valeria Menchise  1 , Giuseppina De Simone, Tullia Tedeschi, Roberto Corradini, Stefano Sforza, Rosangela Marchelli, Domenica Capasso, Michele Saviano, Carlo Pedone
Affiliations

Insights into peptide nucleic acid (PNA) structural features: the crystal structure of a D-lysine-based chiral PNA-DNA duplex

Valeria Menchise et al. Proc Natl Acad Sci U S A. .

Abstract

Peptide nucleic acids (PNAs) are oligonucleotide analogues in which the sugar-phosphate backbone has been replaced by a pseudopeptide skeleton. They bind DNA and RNA with high specificity and selectivity, leading to PNA-RNA and PNA-DNA hybrids more stable than the corresponding nucleic acid complexes. The binding affinity and selectivity of PNAs for nucleic acids can be modified by the introduction of stereogenic centers (such as D-Lys-based units) into the PNA backbone. To investigate the structural features of chiral PNAs, the structure of a PNA decamer containing three D-Lys-based monomers (namely H-GpnTpnApnGpnAdlTdlCdlApnCpnTpn-NH2, in which pn represents a pseudopeptide link and dl represents a D-Lys analogue) hybridized with its complementary antiparallel DNA has been solved at a 1.66-A resolution by means of a single-wavelength anomalous diffraction experiment on a brominated derivative. The D-Lys-based chiral PNA-DNA (LPD) heteroduplex adopts the so-called P-helix conformation. From the substantial similarity between the PNA conformation in LPD and the conformations observed in other PNA structures, it can be concluded that PNAs possess intrinsic conformational preferences for the P-helix, and that their flexibility is rather restricted. The conformational rigidity of PNAs is enhanced by the presence of the chiral centers, limiting the ability of PNA strands to adopt other conformations and, ultimately, increasing the selectivity in molecular recognition.

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Figures

Fig. 1.
Fig. 1.
Chemical structures of PNA and DNA oligomers.
Fig. 2.
Fig. 2.
(A) The PNA sequence containing three d-Lys-based PNA monomers (chiral box). (B) The PNA decamer containing the chiral box hybridized with its complementary antiparallel DNA strand.
Fig. 3.
Fig. 3.
(A) Stereoview of d-Lys-based chiral PNA–DNA double-helix structure. (B) View down the helix axis. The DNA strand is shown in blue, and the PNA strand is shown in red. The image was generated by using bobscript (38).
Fig. 4.
Fig. 4.
Simulated annealing omit |2Fo – Fc| electron density map, computed at 1.66 Å and contoured at 1.0 σ.(A) Representative Tdl6–A5 base pair engaged in Watson–Crick hydrogen bonds. (B) DNA residue T6 and C7 with the sugar moieties in the C3′-endo and C2′-endo conformation, respectively. The image was generated by using bobscript (38).
Fig. 5.
Fig. 5.
Crystal-packing details. (A) A continuous base-pair stacking formed between the molecule in the asymmetric unit (in red) and a symmetry-related one (in blue). (B) Intermolecular electrostatic interactions occurring between d-Lys side chains of residues Adl5, Tdl6, and Cdl7 and phosphate groups of residues T3*, G4*, A5*, and T6*. The monomers with asterisks are related to the asymmetric unit by a 31 axis followed by a translation along the [1 1 0] direction. Water molecules are shown in dark red. The image was generated by using bobscript (38).
Fig. 6.
Fig. 6.
Stereoview of residue Tdl6, showing the interaction between the hydrogen atom (in yellow) bound to the chiral center and the C3′ atom. The image was generated by using bobscript (38).
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References

    1. Nielsen, P. E., Egholm, M., Berg, R. H. & Buchardt, O. (1991) Science 254, 1497–1500. - PubMed
    1. Egholm, M., Buchardt, O., Christensen, L., Behrens, C., Freier, S. M., Driver, D. A., Berg, R. H., Kim, S. K., Norden, B. & Nielsen, P. E. (1993) Nature 365, 566–568. - PubMed
    1. Ulhmann, E., Peyman, A., Breipohl, G. & Will, D. W. (1998) Angew. Chem. Int. Ed. Engl. 37, 2796–2893. - PubMed
    1. Nielsen, P. E. (2000) Curr. Opin. Mol. Ther. 2, 282–287. - PubMed
    1. Ray, A. & Norden, B. (2000) FASEB J. 14, 1041–1060. - PubMed

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