The peptide nucleic acids (PNAs): a new generation of probes for genetic and cytogenetic analyses

Paulasova, Pétra; Pellestor, Franck

doi:10.1016/j.anngen.2004.07.001

Cited by 71 publications

(53 citation statements)

References 39 publications

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“…In PNAs the pseudo-peptide backbone is composed of N-(2-aminoethyl)glycine units (24). PNAs are resistant to both nucleases and proteases (25)(26)(27) and, more importantly, hybridize with high affinity to complementary sequences of single-stranded RNA and DNA, forming Watson-Crick double helices (28)(29)(30)(31). For these reasons, PNAs were found to be excellent candidates for antisense and antigene therapies (32)(33)(34).…”

Section: Peptide Nucleic Acids Targeting Mir-221 Modulate P27mentioning

confidence: 99%

Peptide nucleic acids targeting miR-221 modulate p27Kip1 expression in breast cancer MDA-MB-231 cells

Brognara

Fabbri

Aimi

et al. 2012

International Journal of Oncology

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Abstract. The activity of a peptide nucleic acid (PNA) targeting cancer-associated microRNA-221 is described. PNAs against miR-221 were designed in order to bind very efficiently to the target RNA strand and to undergo efficient uptake in the cells. A polyarginine-PNA conjugate targeted against miR-221 (Rpep-PNA-a221) showed both very high affinity for RNA and efficient cellular uptake without the addition of transfection reagents. Unmodified PNA with the same sequence displayed RNA binding, but cellular uptake was very poor. Consistently, only Rpep-PNA-a221 strongly inhibited miR-221. Targeting miR-221 by PNA resulted in i) lowering of the hybridization levels of miR-221 measured by RT-qPCR, ii) upregulation of p27 Kip1 gene expression, measured by RT-qPCR and western blot analysis. The major conclusion of this study is that efficient delivery of anti-miR PNA through a suitable peptide carrier (Rpep-PNA-a221) leads to inhibition of miR-221 activity, altering the expression of miR-221-regulated functions in breast cancer cells.

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Section: Peptide Nucleic Acids Targeting Mir-221 Modulate P27mentioning

confidence: 99%

Peptide nucleic acids targeting miR-221 modulate p27Kip1 expression in breast cancer MDA-MB-231 cells

Brognara

Fabbri

Aimi

et al. 2012

International Journal of Oncology

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“…The detection of single base pair mutations in circulating DNA requires a very sensitive assay because the frequency of circulating B-RAFsmt DNA will be low. PNAs and LNAs are high-affinity DNA synthetic analogues that hybridize with complementary DNA (20). PNAs have N-(2-aminoethyl)-glycine units as backbones.…”

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confidence: 99%

Utility of Circulating B-RAF DNA Mutation in Serum for Monitoring Melanoma Patients Receiving Biochemotherapy

Shinozaki

O’Day

Kitago

et al. 2007

Clinical Cancer Research

150

115

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Purpose: Somatic B-RAF gene mutation has been identified in many malignancies and detected at a high frequency in cutaneous malignant melanoma. However, the significance of the B-RAF mutation (B-RAFmt) in terms of its prognostic and predictive capabilities for treatment response or disease outcome is not known. We hypothesized that circulating serum B-RAFmt (B-RAFsmt) at V600E, detected in serum, predicts response in melanoma patients receiving concurrent biochemotherapy. Experimental Design: A real-time clamp quantitative reverse transcription-PCR assay was designed to assess B-RAFsmt by peptide nucleic acid clamping and a locked nucleic acid hybrid probe. Normal (n = 18) and American Joint Committee on Cancer stage I to IV melanoma patients (n = 103) were evaluated. These included stage IV patients (n = 48) with blood drawn before and after biochemotherapy. Patients were classified as biochemotherapy responders or nonresponders. Responders (n = 24) had a complete or partial response following biochemotherapy; nonresponders (n = 24) developed progressive disease. Results: Of the103 melanoma patients, 38 (37%) had B-RAFsmt DNA, of which11of 34 (32%) were stage I or II, and 27 of 69 (39%) were stage III or IV. Of the 48 biochemotherapy patients,10 of 24 (42%) patients were positive for the B-RAFsmt in the respective responder and nonresponder groups before treatment. After biochemotherapy, B-RAFsmt was detected in only 1 of 10 patients (10%) in the responder group and 7 of 10 patients (70%) in the nonresponder group. B-RAFsmt is associated with significantly worse (P = 0.039) overall survival in patients receiving biochemotherapy. Conclusion: These studies show the presence and utility of circulating B-RAFsmt DNA in melanoma patients.

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“…However, NMP is ineffective in increasing antibiotic susceptibility of P. aeruginosa (Coban et al 2009). Notably, antisense peptide nucleic acids (PNAs) are synthetic homologues of nucleic acids that bind complementary DNA and RNA sequences with very high specificity (Paulasova and Pellestor 2004).…”

Section: Efflux Pump Inhibitorsmentioning

confidence: 99%

Anti-virulence Strategies to Target Bacterial Infections

Mühlen

Dersch

2015

Current Topics in Microbiology and Immunology

142

139

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Resistance of important bacterial pathogens to common antimicrobial therapies and the emergence of multidrug-resistant bacteria is increasing at an alarming rate and constitutes one of our greatest challenges in the combat of bacterial infection and accompanied diseases. Given the current shortage of effective drugs, lack of successful prevention measures and only a few new antibiotics in the clinical pipeline demands the development of novel treatment options and alternative antimicrobial therapies. Our increasing understanding of bacterial virulence strategies and the induced molecular pathways of the infectious disease provide novel opportunities to target and interfere with crucial pathogenicity factors or virulence-associated traits of the bacteria while bypassing the evolutionary pressure on the bacterium to develop resistance. In the past decade, numerous new bacterial targets for anti-virulence therapies have been identified, and structure-based tailoring of intervention strategies as well as screening assays for small molecule inhibitors of such pathways were successfully established. In this chapter, we will take a closer look at the bacterial virulence-related factors and processes that present promising targets for antivirulence therapies, recently discovered inhibitory substances and their promises and discuss the challenges and problems that have to be faced.

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The peptide nucleic acids (PNAs): a new generation of probes for genetic and cytogenetic analyses

Cited by 71 publications

References 39 publications

Peptide nucleic acids targeting miR-221 modulate p27Kip1 expression in breast cancer MDA-MB-231 cells

Peptide nucleic acids targeting miR-221 modulate p27Kip1 expression in breast cancer MDA-MB-231 cells

Utility of Circulating B-RAF DNA Mutation in Serum for Monitoring Melanoma Patients Receiving Biochemotherapy

Anti-virulence Strategies to Target Bacterial Infections

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