Peptide nucleic acid (PNA). A DNA mimic with a pseudopeptide backbone

Nielsen, Peter E.; Haaima, Gerald

doi:10.1039/cs9972600073

Cited by 223 publications

(149 citation statements)

References 101 publications

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“…The sodium salt of the deoxyoligonucleotid, [d(G 1 A 2 C 3 G 4 G 5 C 6 C 7 G 8 T 9 C 10 ) 2 ], was purchased from Oswel DNA Service and purified with ion-exchange chromatography, desalted and paramagnetic impurities were removed using a Chelex 100 column (Sigma-Aldrich). 4 were added in five steps the duplex sample to reach a 1:2 ratio. This ratio was selected so that no precipitation should occur.…”

Section: Methodsmentioning

confidence: 99%

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Interaction between a DNA oligonucleotide and a dinuclear iron(II) supramolecular cylinder; an NMR and molecular dynamics study

et al. 2002

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Section: Methodsmentioning

confidence: 99%

“…Oligonucleotides (synthetic and natural) can selectively recognize DNA by forming triplexes through binding in the major groove [3] and neutral oligonucleotide analogues (e.g. PNAs) can achieve similar effects, although more commonly they achieve sequence selectivity through strand displacement [4].…”

Section: Introductionmentioning

confidence: 99%

Interaction between a DNA oligonucleotide and a dinuclear iron(II) supramolecular cylinder; an NMR and molecular dynamics study

et al. 2002

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“…PNA hybridizes to complementary DNA, RNA or PNA oligomer sequences through Watson and Crick base pairing and helix formation (Egholm et al, 1993 ;Wittung et al, 1994 ;Jensen et al, 1997). The peptide backbone provides improved hybridization affinity and specificity properties (Egholm et al, 1993 ;Jensen et al, 1997), resistance to enzymic degradation (Demidov et al, 1994) and access to a variety of chemical modifications (Nielsen & Haaima, 1997 ;Pu$ schl et al, 1998). For antisense applications, target-bound PNA can hinder the activities of DNA and RNA polymerases, reverse transcriptase, telomerase and the ribosome (Hanvey et al, 1992 ;Knudsen & Nielsen, 1996 ;Good & Nielsen, 1998a).…”

Section: Introductionmentioning

confidence: 99%

Antisense PNA effects in Escherichia coli are limited by the outer-membrane LPS layer

et al. 2000

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Antisense peptide nucleic acids (PNAs) can inhibit Escherichia coli gene expression and cell growth through sequence-specific RNA binding, and this opens possibilities for novel anti-infective agents and tools for microbial functional genomics. However, the cellular effects of PNAs are limited relative to effects in cell extracts, presumably because of cell barrier components such as the outer-membrane lipopolysaccharide (LPS) layer or drug efflux pumps, both of which function to exclude antibiotics and other foreign molecules. To evaluate the importance of such cellular factors on PNA effects, the authors developed a positive assay for antisense inhibition by targeting the lac operon repressor and compared PNA susceptibilities in mutant and wild-type E. coli by assessing lacZ induction. Strains with defective LPS (AS19 and D22) were more permeable to the antibiotic nitrocefin and more susceptible to PNA than the wild-type. Also, PNA potency was improved in wild-type cells grown in the presence of certain cell-wall-permeabilizing agents. In contrast, the activities of the Acr and Emr drug efflux pumps were not found to affect PNA susceptibility. The results show that the LPS layer is a major barrier against cell entry, but PNAs that can enter E. coli are likely to remain active inside cells.

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“…Neutral oligonucleotide analogues (e.g., peptide nucleic acids) can achieve similar effects, although more commonly they achieve sequence selectivity through strand displacement (5).…”

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confidence: 99%

Intramolecular DNA coiling mediated by metallo-supramolecular cylinders: Differential binding of P and M helical enantiomers

Meistermann

Moreno

Prieto

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

185

119

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We have designed a synthetic tetracationic metallo-supramolecular cylinder that targets the major groove of DNA with a binding constant in excess of 10 7 M ؊1 and induces DNA bending and intramolecular coiling. The two enantiomers of the helical molecule bind differently to DNA and have different structural effects. We report the characterization of the interactions by a range of biophysical techniques. The M helical cylinder binds to the major groove and induces dramatic intramolecular coiling. The DNA bending is less dramatic for the P enantiomer.W hile DNA encodes the essential blueprint for life, within biological systems its structure and function is regulated by proteins. In the postgenomic environment the goal is to understand the processing of the genetic code and how to stimulate or prevent this processing. To achieve this end a variety of different types of molecular tools will be required that recognize the genetic code in a sequence-selective fashion. Within biological systems, sequencespecific code recognition is generally achieved by the surface motifs of proteins, which generally interact noncovalently with the major groove of DNA (1-3). The major groove is particularly attractive for DNA recognition because the size and shape of the major groove of B-DNA varies most with base sequence. For example, transcriptional regulators often involve cylindrical binding units, such as ␣-helices or zinc fingers, that insert into the major groove and may kink the DNA (1-3).Oligonucleotides (synthetic and natural) can selectively recognize DNA by forming triplexes through binding in the major groove (4). Neutral oligonucleotide analogues (e.g., peptide nucleic acids) can achieve similar effects, although more commonly they achieve sequence selectivity through strand displacement (5).Such biomacromolecule recognition of DNA contrasts with synthetic small molecule recognition agents. Synthetic molecules that achieve sequence selectivity include well-known minor groove binders such as amide-linked imidazole͞pyrole oligomers and polymers (6), which in common with many small-molecule DNA-binding agents target the minor groove (7). Alternatively small molecules can act by means of intercalation (8, 9). Synthetic agents that target the major groove of DNA with recognition through noncovalent surface motifs have the potential to be a powerful new tool in the armory of reagents that is being developed to tackle the postgenomic challenge. However, to date little progress has been made in this direction, caused in large part by the size of the molecular surfaces required.DNA binding by metal complexes through formation of metal-ligand bonds (e.g., cisplatin) has been extensively studied and usually focuses on binding to N7 of G and A residues (ref. 10 and references therein). By contrast, noncovalent binding of metal complexes to DNA is a less well-developed area and has primarily centered around approximately spherical ruthenium polypyridyl complexes, complexes bearing planar intercalating units, or combinations thereof ...

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Peptide nucleic acid (PNA). A DNA mimic with a pseudopeptide backbone

Cited by 223 publications

References 101 publications

Interaction between a DNA oligonucleotide and a dinuclear iron(II) supramolecular cylinder; an NMR and molecular dynamics study

Interaction between a DNA oligonucleotide and a dinuclear iron(II) supramolecular cylinder; an NMR and molecular dynamics study

Antisense PNA effects in Escherichia coli are limited by the outer-membrane LPS layer

Intramolecular DNA coiling mediated by metallo-supramolecular cylinders: Differential binding of P and M helical enantiomers

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