Insights on chiral, backbone modified peptide nucleic acids: Properties and biological activity

Moccia, Maria; Adamo, Mauro F. A.

doi:10.1080/1949095x.2015.1107176

Cited by 28 publications

(37 citation statements)

References 121 publications

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“…(KFF) 3 K-acpP inhibits in vitro synthesis of AcpP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] -GFP Next, we investigated whether (KFF) 3 K-acpP inhibits acpP translation, as would be expected from the sequence-complementarity of the PNA to the translational start site of its target mRNA. To this aim, we applied a cell-free in vitro translation system.…”

Section: (Kff) 3 K-acpp Mediates Bactericidal Effects In Upec 536mentioning

confidence: 99%

“…These properties allow the use of short oligomers -usually in the range of 9-12mers, to block a target (6)(7)(8). The capacity of PNA to base-pair with complementary sequences makes them bona fide antisense drugs, with the ability to inhibit gene expression both on the transcriptional (9)(10)(11)(12) and posttranscriptional level (6,8,13,14). PNAs are generally designed to be complementary to the translation start site of a target mRNA and sterically block ribosome binding and initiation of translation (1,6,13).…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive analysis of PNA-based antisense antibiotics targeting various essential genes in uropathogenic Escherichia coli

Popella

Jung

Thao

et al. 2022

Preprint

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Antisense peptide nucleic acids (PNAs) that target mRNAs of essential bacterial genes exhibit specific bactericidal effects in several microbial species, but our mechanistic understanding of PNA activity and their target gene spectrum is limited. Here, we present a systematic analysis of PNAs targeting eleven essential genes with varying expression levels in uropathogenic Escherichia coli (UPEC). We demonstrate that UPEC is susceptible to killing by peptide-conjugated PNAs, especially when targeting the widely-used essential gene acpP. Our evaluation yields three additional promising target mRNAs for effective growth inhibition, i.e., dnaB, ftsZ, and rpsH. The analysis also shows that transcript abundance does not predict target vulnerability and that PNA-mediated growth inhibition is not universally associated with target mRNA depletion. Global transcriptomic analyses further reveal PNA sequence-dependent but also -independent responses, including the induction of envelope stress response pathways. Importantly, we show that the growth inhibitory capacity of 9mer PNAs is generally as effective as their 10mer counterparts. Overall, our systematic comparison of a range of PNAs targeting mRNAs of different essential genes in UPEC suggests important features for PNA design, reveals a general bacterial response to PNA conjugates and establishes the feasibility of using PNA antibacterials to combat UPEC.

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Section: (Kff) 3 K-acpp Mediates Bactericidal Effects In Upec 536mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of PNA-based antisense antibiotics targeting various essential genes in uropathogenic Escherichia coli

Popella

Jung

Thao

et al. 2022

Preprint

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“…[ 52 ] As such, chiral PNA backbones with modifications at the α‐, β‐, and γ‐positions have been developed, each possessing unique oligomer binding and conformational properties. [ 53 ]…”

Section: Modifications Of Pna: Improving Gene Targetingmentioning

confidence: 99%

Peptide nucleic acids and their role in gene regulation and editing

2021

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The unique properties of peptide nucleic acid (PNA) makes it a desirable candidate to be used in therapeutic and biotechnological interventions. It has been broadly utilized for numerous applications, with a major focus in regulation of gene expression, and more recently in gene editing. While the classic PNA design has mainly been employed to date, chemical modifications of the PNA backbone and nucleobases provide an avenue to advance the technology further. This review aims to discuss the recent developments in PNA based gene manipulation techniques and the use of novel chemical modifications to improve the current state of PNA mediated gene targeting.

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“…PNAs are DNA/RNA analogs possessing a pseudo-peptide backbone made of N-(2 aminoethyl) glycine (aeg) motif to replace the sugar phosphate one (Nielsen et al, 1991). These chemical entities may provide a convenient platform for the preparation of specific sequences, as they combine desirable hybridization properties (Egholm et al, 1993;Nielsen et al, 1993;Moccia et al, 2016), robust synthesis, ease of conjugation to cell penetrating peptides (CPP) (Lee et al, 2014), and high biochemical stability (Demidov et al, 1994). In our previous study (Piacenti et al, 2019), PNA sequences were designed using miRNA-34a structure as a model template.…”

Section: Introductionmentioning

confidence: 99%

Structural Insights on Tiny Peptide Nucleic Acid (PNA) Analogues of miRNA-34a: An in silico and Experimental Integrated Approach

et al. 2020

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In the present work, structural features of the interaction between peptide nucleic acid (PNA)-based analogs of the tumor-suppressor microRNA-34a with both its binding sites on MYCN mRNA were investigated. In particular, the region from base 1 to 8 (“seed” region) of miR-34a was reproduced in the form of an 8-mer PNA fragment (tiny PNA), and binding to target 3'UTR MYCN mRNA, was studied by a seldom reported and detailed NMR characterization, providing evidence for the formation of anti-parallel duplexes with a well-organized structural core. The formation of PNA-3'UTR duplexes was also confirmed by Circular Dichroism, and their melting curves were measured by UV spectroscopy. Nevertheless, this study offered a valuable comparison between molecular dynamics predictions and experimental evidence, which showed great correlation. Preliminary uptake assays were carried out in Neuroblastoma Kelly cells, using short peptide conjugates as carriers and FITC fluorescent tag for subcellular localization. Moderate internalization was observed without the use of transfecting agents. The reported results corroborate the interest toward the design and development of chimeric PNA/RNA sequences as effective RNA-targeting agents.

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Insights on chiral, backbone modified peptide nucleic acids: Properties and biological activity

Cited by 28 publications

References 121 publications

Comprehensive analysis of PNA-based antisense antibiotics targeting various essential genes in uropathogenic Escherichia coli

Comprehensive analysis of PNA-based antisense antibiotics targeting various essential genes in uropathogenic Escherichia coli

Peptide nucleic acids and their role in gene regulation and editing

Structural Insights on Tiny Peptide Nucleic Acid (PNA) Analogues of miRNA-34a: An in silico and Experimental Integrated Approach

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