PNA-nucleic acid complexes. Structure, stability and dynamics

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).

[1]  B. Nordén,et al.  Kinetics for hybridization of peptide nucleic acids (PNA) with DNA and RNA studied with the BIAcore technique. , 1997, Biochemistry.

[2]  Peter E. Nielsen,et al.  Peptide Nucleic Acids (PNAs) Containing Thymine Monomers Derived from Chiral Amino Acids: Hybridization and Solubility Properties of D‐Lysine PNA , 1996 .

[3]  B. Nordén,et al.  Direct observation of strand invasion by peptide nucleic acid (PNA) into double-stranded DNA , 1996 .

[4]  P. Nielsen,et al.  Enhanced peptide nucleic acid binding to supercoiled DNA: possible implications for DNA "breathing" dynamics. , 1996, Biochemistry.

[5]  Peter E. Nielsen,et al.  Ionic Effects on the Stability and Conformation of Peptide Nucleic Acid Complexes , 1996 .

[6]  P. Nielsen,et al.  Solution structure of a peptide nucleic acid–DNA duplex , 1996, Nature Structural Biology.

[7]  Peter E. Nielsen,et al.  STRAND DISPLACEMENT BINDING OF A DUPLEX-FORMING HOMOPURINE PNA TO A HOMOPYRIMIDINE DUPLEX DNA TARGET , 1996 .

[8]  L. Betts,et al.  A Nucleic Acid Triple Helix Formed by a Peptide Nucleic Acid-DNA Complex , 1995, Science.

[9]  B. Nordén,et al.  Induced Chirality in PNA-PNA Duplexes , 1995 .

[10]  S. Wendeborn,et al.  Backbone modifications in oligonucleotides and peptide nucleic acid systems. , 1995, Current opinion in structural biology.

[11]  P. Hanawalt,et al.  Presence of negative torsional tension in the promoter region of the transcriptionally poised dihydrofolate reductase gene in vivo. , 1995, Nucleic acids research.

[12]  B. Nordén,et al.  Phospholipid membrane permeability of peptide nucleic acid , 1995, FEBS letters.

[13]  R. H. Berg,et al.  Solid‐Phase synthesis of peptide nucleic acids , 1995, Journal of peptide science : an official publication of the European Peptide Society.

[14]  V V Demidov,et al.  Kinetics and mechanism of polyamide ("peptide") nucleic acid binding to duplex DNA. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Brown,et al.  Impact of biophysical parameters on the biological assessment of peptide nucleic acids, antisense inhibitors of gene expression , 1995 .

[16]  M. Egholm,et al.  Efficient pH-independent sequence-specific DNA binding by pseudoisocytosine-containing bis-PNA. , 1995, Nucleic acids research.

[17]  D. Patel,et al.  DNA triplexes: solution structures, hydration sites, energetics, interactions, and function. , 1994, Biochemistry.

[18]  V V Demidov,et al.  Stability of peptide nucleic acids in human serum and cellular extracts. , 1994, Biochemical pharmacology.

[19]  M. Egholm,et al.  Evidence for (PNA)2/DNA triplex structure upon binding of PNA to dsDNA by strand displacement , 1994, Journal of molecular recognition : JMR.

[20]  B. Nordén,et al.  Structural characterization of PNA-DNA duplexes by NMR. Evidence for DNA in a B-like conformation. , 1994, Biochemistry.

[21]  D. G. Davis,et al.  NMR solution structure of a peptide nucleic acid complexed with RNA. , 1994, Science.

[22]  R. Griffey,et al.  Molecular dynamics and NMR studies of single-stranded PNAs , 1994 .

[23]  Peter E. Nielsen,et al.  DNA-like double helix formed by peptide nucleic acid , 1994, Nature.

[24]  M. Egholm,et al.  Single base pair mutation analysis by PNA directed PCR clamping. , 1993, Nucleic acids research.

[25]  L E Babiss,et al.  Strand-invasion of duplex DNA by peptide nucleic acid oligomers. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[26]  O. Almarsson,et al.  Peptide nucleic acid (PNA) conformation and polymorphism in PNA-DNA and PNA-RNA hybrids. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Peter E. Nielsen,et al.  PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules , 1993, Nature.

[28]  M. Egholm,et al.  Right-handed triplex formed between peptide nucleic acid PNA-T8 and poly(dA) shown by linear and circular dichroism spectroscopy , 1993 .

[29]  M. Egholm,et al.  DNA unwinding upon strand-displacement binding of a thymine-substituted polyamide to double-stranded DNA. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[30]  R. Sinden,et al.  Stably maintained microdomain of localized unrestrained supercoiling at a Drosophila heat shock gene locus. , 1993, The EMBO journal.

[31]  J. Bisi,et al.  Antisense and antigene properties of peptide nucleic acids. , 1992, Science.

[32]  Peter E. Nielsen,et al.  Peptide nucleic acids (PNA) : oligonucleotide analogues with an achiral peptide backbone , 1992 .

[33]  M. Egholm,et al.  Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. , 1991, Science.

[34]  K. Sharp,et al.  Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons , 1991, Proteins.

[35]  P. Dervan,et al.  Sequence-specific cleavage of double helical DNA by triple helix formation. , 1987, Science.

[36]  P. Nielsen.  Peptide nucleic acids: a new dimension to peptide libraries and aptamers. , 1996, Methods in enzymology.

[37]  P. Nielsen,et al.  Peptide nucleic acids (PNA): synthesis, properties and potential applications. , 1996, Bioorganic & medicinal chemistry.

[38]  P. Nielsen,et al.  DNA analogues with nonphosphodiester backbones. , 1995, Annual review of biophysics and biomolecular structure.

[39]  Michael Griffith,et al.  SINGLE AND BIS PEPTIDE NUCLEIC ACIDS AS TRIPLEXING AGENTS : BINDING AND STOICHIOMETRY , 1995 .

[40]  M. Egholm,et al.  Peptide nucleic acid (PNA). A DNA mimic with a peptide backbone. , 1994, Bioconjugate chemistry.

[41]  B. Nordén,et al.  Interactions of DNA binding ligands with PNA-DNA hybrids. , 1994, Nucleic acids research.