Anti-gene peptide nucleic acid targeted to proviral HIV-1 DNA inhibits in vitro HIV-1 replication

Pesce, Caterina Delfina; Bolacchi, Francesca; Bongiovanni, Barbara; Cisotta, Federica; Capozzi, M.; Diviacco, Silvia; Quadrifoglio, Franco; Mango, Ruggiero; Novelli, Giuseppe; Mossa, Giuseppe; Esposito, Claudio; Ombres, Domenico; Rocchi, G; Bergamini, Alberto

doi:10.1016/j.antiviral.2004.12.001

Cited by 13 publications

(6 citation statements)

References 52 publications

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“…Some examples of inhibition of the replication process (Figure 5C) have also been reported (116,117). DNA polymerase elongation can be inhibited by in vitro triplex-formation upstream (118) or downstream (119,120) the initiation site.…”

Section: In Vitro Applications Of Tfos As Gene Modulatorsmentioning

confidence: 53%

The triple helix: 50 years later, the outcome

Duca

Vekhoff

Oussedik

et al. 2008

Nucleic Acids Research

317

269

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Triplex-forming oligonucleotides constitute an interesting DNA sequence-specific tool that can be used to target cleaving or cross-linking agents, transcription factors or nucleases to a chosen site on the DNA. They are not only used as biotechnological tools but also to induce modifications on DNA with the aim to control gene expression, such as by site-directed mutagenesis or DNA recombination. Here, we report the state of art of the triplex-based anti-gene strategy 50 years after the discovery of such a structure, and we show the importance of the actual applications and the main challenges that we still have ahead of us.

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Section: In Vitro Applications Of Tfos As Gene Modulatorsmentioning

confidence: 53%

The triple helix: 50 years later, the outcome

Duca

Vekhoff

Oussedik

et al. 2008

Nucleic Acids Research

317

269

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“…Peptide nucleic acids (PNA) are synthetic nucleic acid analogs where the usual phosphate backbone in DNA or RNA is replaced by N -(2-aminoethyl)-glycine units (see Figure ). , PNAs can form duplexes with DNA, RNA, or other PNAs as well as triplexes with DNA, binding via complementary Watson–Crick or Hoogsteen base pair formation and assuming structures similar to regular nucleic acids. − PNA-DNA complexes can be more stable than DNA-DNA and DNA-RNA complexes so that DNA strand invasion in the presence of PNA with a complementary base sequence is likely. , This has led to an interest in developing PNAs for a number of biotechnology applications including antisense and antigene actions, e.g., as inhibitors of bacterial translation by targeting mRNA , or rRNA, , as inhibitors of viral replication or in gene therapies targeting host DNA − or microRNAs. , …”

Section: Introductionmentioning

confidence: 99%

Improved Force Fields for Peptide Nucleic Acids with Optimized Backbone Torsion Parameters

Jasiński

Feig

Trylska

2018

J. Chem. Theory Comput.

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Peptide nucleic acids are promising nucleic acid analogs for antisense therapies as they can form stable duplex and triplex structures with DNA and RNA. Computational studies of PNA-containing duplexes and triplexes are an important component for guiding their design, yet existing force fields have not been well validated and parametrized with modern computational capabilities. We present updated CHARMM and Amber force fields for PNA that greatly improve the stability of simulated PNA-containing duplexes and triplexes in comparison with experimental structures and allow such systems to be studied on microsecond time scales. The force field modifications focus on reparametrized PNA backbone torsion angles to match high-level quantum mechanics reference energies for a model compound. The microsecond simulations of PNA-PNA, PNA-DNA, PNA-RNA, and PNA-DNA-PNA complexes also allowed a comprehensive analysis of hydration and ion interactions with such systems.

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“…13,14 Polycationic peptides are also frequently conjugated to PNA for use in cellular uptake. [15][16][17] Despite this frequent attachment of amino acids and peptides to PNA probes, there appears to have been few quantitative studies into the effect that these residues have on PNA-DNA duplex stability and sequence specificity. To date, the only studies we are aware of in this field have been with respect to bis-PNA probes for strand invasion and the attachment of short lysine chains to PNA probes for enhancement of cellular uptake.…”

Section: Introductionmentioning

confidence: 99%

Effect of terminal amino acids on the stability and specificity of PNA–DNA hybridisation

et al. 2007

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The effect of various charged or hydrophobic amino acids on the hybridisation of fully complementary and mismatch PNA-DNA duplexes was investigated via UV melting curve analysis. The results described here show that the thermal stability and binding specificity of PNA probes can be modified by conjugation to amino acids and these effects should be considered in experimental design when conjugating PNA sequences to solubility enhancing groups or cell transport peptides. Where stabilisation of a duplex is important, without there being a corresponding need for specific binding to fully complementary targets, the conjugation of multiple lysine residues to the C-terminus of PNA may be the best probe design. If, however, the key is to obtain maximum discrimination between fully complementary and mismatch targets, a replacement of glutamic acid for lysine as the routine solubility enhancing group is recommended.

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Anti-gene peptide nucleic acid targeted to proviral HIV-1 DNA inhibits in vitro HIV-1 replication

Cited by 13 publications

References 52 publications

The triple helix: 50 years later, the outcome

The triple helix: 50 years later, the outcome

Improved Force Fields for Peptide Nucleic Acids with Optimized Backbone Torsion Parameters

Effect of terminal amino acids on the stability and specificity of PNA–DNA hybridisation

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