Hostname: page-component-78c5997874-lj6df Total loading time: 0 Render date: 2024-11-10T05:17:55.111Z Has data issue: false hasContentIssue false

PNA-nucleic acid complexes. Structure, stability and dynamics

Published online by Cambridge University Press:  17 March 2009

Magdalena Eriksson
Affiliation:
Center for Biomolecular Recognition, The Panum Institute, Department of Biochemistry B, Blegdamsvej 3c, DK-2200 Copenhagen N, Denmark
Peter E. Nielsen
Affiliation:
Center for Biomolecular Recognition, The Panum Institute, Department of Biochemistry B, Blegdamsvej 3c, DK-2200 Copenhagen N, Denmark

Extract

Growing interest in gene targeting drugs has inspired the development of a multitude of nucleic acid analogues, many of which feature substitutions in the phosphodiester moiety of the backbone (reviewed by Mesmaeker et al. 1995 and Nielsen, 1995). Peptide nucleic acid (PNA) is an example of a more radical redesign of DNA. The entire sugar-phosphate backbone is substituted by a chain of peptide-like N-(2-aminoethyl)glycine units so that an achiral and uncharged DNA-mimic is obtained (Fig. 1; Nielsen et al. 1991). The synthesis is based on standard peptide chemistry (Christensen et al. 1995) and has been automated. PNA can relatively easily be modified to include modifications of the backbone as well as of the bases (Hyrup & Nielsen, 1996). PNA is chemically stable and, in contrast to natural nucleic acids and peptides, PNA is expected to remain intact in living cells since it is not a substrate for natural hydrolytic enzymes and is not degraded by cell extracts (Demidov et al. 1994).

Type
Research Article
Copyright
Copyright © Cambridge University Press 1996

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Almarson, Ø. & Bruice, T. C. (1993). Peptide nucleic acid (PNA) conformation and polymorphism in PNA–DNA and PNA–RNA hybrids. Proc. Natl. Acad. Sci. USA 90, 95429546.CrossRefGoogle Scholar
Bentin, T. & Nielsen, P. E. (1996). Enhanced peptide nucleic acid (PNA) binding to supercoiled DNA: possible implications for DNA ‘breathing’ dynamics. Biochemistry, in press.CrossRefGoogle Scholar
Betts, L., Josey, J. A., Veal, J. M. & Jordan, S. R. (1995). A nucleic acid triple helix formed by a peptide nucleic acid-DNA complex. Science 270, 18381841.CrossRefGoogle ScholarPubMed
Brown, S. C., Thomson, S. A., Veal, J. M. & Davis, D. G. (1994). NMR solution structure of a peptide nucleic acid complexed with RNA. Science 265, 777780.CrossRefGoogle ScholarPubMed
Chen, S.-M., Mohan, V., Kiely, J. S., Griffith, M. C. & Griffey, R. H. (1994). Molecular dynamics and NMR studies of single-stranded PNAs. Tetrahedron Letters 35, 51055108.CrossRefGoogle Scholar
Cherny, D. Y., Belotserkovskii, B. P., Frank-Kamenetskii, M. D., Egholm, M., Buchardt, O., Berg, R. H. & Nielsen, P. E. (1993). Proc. Natl. Acad. Sci. USA 90, 16671670.CrossRefGoogle Scholar
Christensen, L., Fitzpatrick, R., Gildea, B., Petersen, K. H., Hansen, H. F., Koch, T., Egholm, M., Buchardt, O., Nielsen, P. E., Coull, J. & Berg, R. H. (1995). Solid-phase synthesis of peptide nucleic acids (PNA) J. Peptide Sci. 3, 175183.CrossRefGoogle Scholar
Demidov, V. V., Potaman, V. N., Frank-Kamenetskii, M., Egholm, M., Buchardt, O., Sönnichsen, S. H. & Nielsen, P. E. (1994). Stability of of peptide nucleic acids in human serum and cellular extracts. Biochemical Pharmacology 48, 13101313.CrossRefGoogle ScholarPubMed
Demidov, V. V., Yavnilovich, M. V., Belotserkovskii, B. P., Frank-Kamenetskii, M. & Nielsen, P. E. (1995). Kinetics and mechanism of polyamide (‘peptide’) nucleic acid binding to duplex DNA. Proc. Natl. Acad. Sci. USA 92, 26372641.CrossRefGoogle ScholarPubMed
Egholm, M., Buchardt, O., Nielsen, P. E., & Berg, R. H. (1992). Peptide nucleic acids(PNA). Oligonucleotide analogues with an achiral peptide backbone. Amer. Chem. Soc. 114, 18951897.CrossRefGoogle Scholar
Egholm, M., Buchardt, O., Christensen, L., Behrens, K., Freier, S. M., Driver, D. A., Berg, R. H., Kim, S. K., Nordén, B. & Nielsen, P. E. (1993). PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules. Nature 365, 566568.CrossRefGoogle ScholarPubMed
Egholm, M., Christensen, L., Dueholm, K. L., Buchardt, O., Coull, J. & Nielsen, P. E. (1995). Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA. Nucleic Acids Res. 23, 217222.CrossRefGoogle ScholarPubMed
Eriksson, M. & Nielsen, P. E. (1996). Solution structure of a peptide nucleic acid-DNA duplex. Nature Struct. Biol. 3, 410413.CrossRefGoogle ScholarPubMed
Griffith, M. C., Risen, L. M., Greig, M. J., Lesnik, E. A., Sprankle, K. G., Griffey, R. H.,. Kiely, J. S. & Freier, S. M. (1995). Single and bis peptide nucleic acid as triplexing agents: binding and stoichiometry. J. Amer. Chem. Soc. 117, 831832.CrossRefGoogle Scholar
Haaima, G., Lohse, A., Buchardt, O. & Nielsen, P. E. (1996). Peptide nucleic acids (PNA) containing thymine monomers derived from chiral amino acids. PNAs with increased binding and sequence discrimination. Angewandte Chemie. In press.Google Scholar
Hanvey, J. C., Peffer, N. J., Bisi, J. E., Thomson, S. A., Cadilla, R., JoseyJ, A. J, A., Ricca, D. J., Hassman, C. F., Bonham, M. A., Au, K. G., Carter, S. G., Bruckenstein, D. A., Boyd, A. L., Noble, S. A. & Babiss, L. E. (1992). Antisense and antigene properties of peptide nucleic acids. Science 258, 14811485.CrossRefGoogle ScholarPubMed
Hyrup, B. & Nielsen, P. E. (1996). Peptide nucleic acids (PNA): synthesis, properties and potential applications. Bioorganic & Medicinal Chemistry 4, 523.CrossRefGoogle ScholarPubMed
Jensen, K. K., Ørum, H., Nielsen, P. E. & Nordén, B. (1996). Hybridization kinetics of peptide nucleic acids (PNA) with DNA and RNA studied with BIAcore technique. Submitted manuscript.Google Scholar
Jupe, E. R., Sinden, R. R. & Cartwright, I. L. (1993). Stably maintained microdomain of localized unrestrained supercoiled at a Drosophila heat shock protein locus. EMBO J. 12, 10671075.CrossRefGoogle Scholar
Kim, S. K., Nielsen, P. E., Egholm, M., Buchardt, O., Berg, R. H. & Nordén, B. (1993). Right-handed triplex formed between peptide nucleic acid PNA-T8 and Poly(dA) shown by linear and circular dichroism spectroscopy. J. Am. Chem. Soc. 115, 64776481.CrossRefGoogle Scholar
Leijon, M., Gräslund, A., Nielsen, P. E., Buchardt, O., Nordén, B., Kristensen, S. M. & Eriksson, M. (1994). Structural characterization of PNA–DNA duplexes by NMR. Evidence or DNA in a B-like Conformation. Biochemistry 33, 98209825.CrossRefGoogle ScholarPubMed
Ljungman, M. & Hanawalt, P. C. (1995). Presence of negative torsional tension in the promoter region of the transcriptionally poised dihydrofolate reductase gene in vivo. Nucleic Acids Res. 23, 17821789.CrossRefGoogle ScholarPubMed
Mesmaeker, A. D., Altmann, K.-H., Waldner, A. & Wendeborn, S. (1995). Backbone modifications in oligonucleotides and peptide nucleic acid systems. Current Opinion in Structural Biology 5, 343355.CrossRefGoogle ScholarPubMed
Moser, H. E. & Dervan, P. B. (1987). Sequence specific cleavage of double helical DNA by triple helix formation. Science 238, 645650.CrossRefGoogle ScholarPubMed
Nicholls, A., Sharp, K. A. & Honig, B. H. (1991). Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins 11, 281296.CrossRefGoogle ScholarPubMed
Nielsen, P. E. (1995). DNA analogues with nonphophodiester backbones. Annu. Rev. Biophys. Biomol. Struct. 24, 167183.CrossRefGoogle ScholarPubMed
Nielsen, P. E. (1996). Peptide nucleic acids (PNA). A new dimension to peptide libraries and aptamers. Methods Enzymol. 267, 426433.CrossRefGoogle Scholar
Nielsen, P. E. & Christensen, L. (1996). Strand displacement binding of a duplexforming homopurine PNA to a homopyrimidine duplex DNA target. J. Am. Chem. Soc. 118, 22872288.CrossRefGoogle Scholar
Nielsen, P. E. & Ørum, H. (1995). Peptide nucleic acid (PNA) as new biomolecular tools. In Molecular biology: Current innovations and future trends Horizon Scientific Press, UK, (Griffin, H., ed.) p. 7386.Google Scholar
Nielsen, P. E., Egholm, M., Berg, R. H. & Buchardt, O. (1991). Sequence-selective recognition by strand displacement with a thymine-substituted polyamide. Science 254, 14971500.CrossRefGoogle ScholarPubMed
Nielsen, P. E., Egholm, M. & Buchardt, O. (1994 a). Peptide nucleic acid (PNA). A DNA mimic with a peptide backbone. Bioconjugate Chemistry 5, 37.CrossRefGoogle ScholarPubMed
Nielsen, P. E., Egholm, M. & Buchardt, O. (1994 b). Evidence for (PNA)2/DNA triplex structure upon binding of PNA to dsDNA by strand displacement, j. Mol. Recog. 7, 165170.CrossRefGoogle ScholarPubMed
Noble, S. A., Bonham, M. A., Bisi, J. E., Bruckenstein, D. A., Brown, P. H., Brown, S. C., Cadilla, R., Gaul, M. D., Hanvey, J. C.. et al. (1995). Impact of biophysical parameters on the biological assessment of peptide nucleic acids, antisense inhibitors of gene expression. Drug Development Research 34, 184195.CrossRefGoogle Scholar
Ørum, H., Nielsen, P. E., Egholm, M., Berg, R. H., Buchardt, O.., Stanley, C. (1993). Single base pair mutation analysis by PNA directed PCR clamping. Nucleic Acids Res. 21, 53325336.CrossRefGoogle ScholarPubMed
Peffer, N. J., Hanvey, J. C., Bisi, J. E., Thomson, S. A., Hassman, C. F., Noble, S.A. & Babiss, L. E. (1993). Strand-invasion of duplex DNA by peptide nucleic acid oligomers. Proc. Natl. Acad. Sci. USA 90, 1064810652.CrossRefGoogle ScholarPubMed
Radhakrishnan, I. & Patel, D. J. (1995). DNA triplex: solution structures, hydration sites, energetics, interactions, and function. Biochemistry 33, 1140511416.CrossRefGoogle Scholar
Tomac, S., Sarkar, M., Ratilainen, T., Wittung, P., Nielsen, P. E., Nordén, B. & Gräslund, A. (1996). Iionic effects on the stability and conformation of peptide nucleic acid (PNA) complexes. J. Amer. Chem. Soc. In press.CrossRefGoogle Scholar
Wittung, P., Nielsen, P. E., Buchardt, O., Egholm, M. & Nordén, B. (1994 a). DNA-like double helix formed by peptide nucleic acid. Nature 368, 561563.CrossRefGoogle ScholarPubMed
Wittung, P., Kim, S. K., Buchardt, O., Nielsen, P. E. & Nordén, B. (1994 b). Interactions of DNA binding ligands with PNA-DNA hybrids. Nucleic Acids Res. 22, 53715377.CrossRefGoogle ScholarPubMed
Wittung, P., Eriksson, M., Lyng, R., Nielsen, P. E. & Nordén, B. (1995 a). Induced chirality in PNA–PNA duplexes. J. Amer. Chem. Soc. 117, 1016710173.CrossRefGoogle Scholar
Wittung, P., Kajanus, J., Edwards, K., Nielsen, P. E., Nordén, B. & Malmström, B. G. (1995 b). Phospholopid membrane permeability of peptide nucleic acid. FEBS Letters 365, 2729.CrossRefGoogle Scholar
Wittung, P., Nielsen, P. E. & Nordén, B. (1996). Direct observation od strand invasion by peptide nucleic acid (PNA) into double-stranded DNA. J. Amer. Chem. Soc. 118, 70497054.CrossRefGoogle Scholar