Polyanionic Carboxyethyl Peptide Nucleic Acids (ce-PNAs): Synthesis and DNA Binding

Kirillova, Yu. G.; Boyarskaya, N. P.; Dezhenkov, A. V.; Tankevich, Mariya; Prokhorov, I. A.; Varizhuk, Anna M.; Eremin, S. V.; Esipov, D. S.; Smirnov, Igor P.; Pozmogova, Galina E.

doi:10.1371/journal.pone.0140468

Cited by 16 publications

(17 citation statements)

References 73 publications

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“…The negative charges allowed cationic lipid-mediated delivery of PNAs to HeLa cells achieving sub-nanomolar antisense activity [91]. More recent studies introduced sulphate and carboxylate groups at the γ-position of PNA backbone (Figure 5) but neither modification showed promising hybridization profiles or improved cellular uptake [92,93].…”

Section: Conformationally Constrained Backbonesmentioning

confidence: 99%

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

Brodyagin

Katkevičs

Kotikam

et al. 2021

Beilstein J. Org. Chem.

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Peptide nucleic acid (PNA) is arguably one of the most successful DNA mimics, despite a most dramatic departure from the native structure of DNA. The present review summarizes 30 years of research on PNA’s chemistry, optimization of structure and function, applications as probes and diagnostics, and attempts to develop new PNA therapeutics. The discussion starts with a brief review of PNA’s binding modes and structural features, followed by the most impactful chemical modifications, PNA enabled assays and diagnostics, and discussion of the current state of development of PNA therapeutics. While many modifications have improved on PNA’s binding affinity and specificity, solubility and other biophysical properties, the original PNA is still most frequently used in diagnostic and other in vitro applications. Development of therapeutics and other in vivo applications of PNA has notably lagged behind and is still limited by insufficient bioavailability and difficulties with tissue specific delivery. Relatively high doses are required to overcome poor cellular uptake and endosomal entrapment, which increases the risk of toxicity. These limitations remain unsolved problems waiting for innovative chemistry and biology to unlock the full potential of PNA in biomedical applications.

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Section: Conformationally Constrained Backbonesmentioning

confidence: 99%

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

Brodyagin

Katkevičs

Kotikam

et al. 2021

Beilstein J. Org. Chem.

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“…Their backbone is neutral and generates no electrostatic repulsions, allowing a remarkable stability toward complementary NAs. They are also able to interact with both, DNA (Kirillova et al, 2015) and RNA (Sato et al, 2016) duplexes and PNAs derivatives can be obtained by chemical modification for enhanced affinity (Annoni et al, 2016) and solubility (Sahu et al, 2011). Phosphorodiamidate morpholino oligos (PMO) are also synthetic DNA analogs that possess a neutral backbone of morpholine rings, which not only provides higher solubility in aqueous solutions than PNAs, but also more flexibility in length (Liao et al, 2017).…”

Section: Nucleic-acid Based Label-free Optical Biosensorsmentioning

confidence: 99%

Advanced Evanescent-Wave Optical Biosensors for the Detection of Nucleic Acids: An Analytic Perspective

et al. 2019

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Evanescent-wave optical biosensors have become an attractive alternative for the screening of nucleic acids in the clinical context. They possess highly sensitive transducers able to perform detection of a wide range of nucleic acid-based biomarkers without the need of any label or marker. These optical biosensor platforms are very versatile, allowing the incorporation of an almost limitless range of biorecognition probes precisely and robustly adhered to the sensor surface by covalent surface chemistry approaches. In addition, their application can be further enhanced by their combination with different processes, thanks to their integration with complex and automated microfluidic systems, facilitating the development of multiplexed and user-friendly platforms. The objective of this work is to provide a comprehensive synopsis of cutting-edge analytical strategies based on these label-free optical biosensors able to deal with the drawbacks related to DNA and RNA detection, from single point mutations assays and epigenetic alterations, to bacterial infections. Several plasmonic and silicon photonic-based biosensors are described together with their most recent applications in this area. We also identify and analyse the main challenges faced when attempting to harness this technology and how several innovative approaches introduced in the last years manage those issues, including the use of new biorecognition probes, surface functionalization approaches, signal amplification and enhancement strategies, as well as, sophisticated microfluidic solutions.

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“…Recently, it was shown by researchers that γ-S-carboxyethyl-T10 PNA formed a stable PNA 2 -DNA triplex as compared to its α-analogue (Kirillova et al, 2015). PNAs are also found to form stable triplex invasion complexes, and also conventional triplexes with the dsDNA target.…”

Section: Diverse Applicationsmentioning

confidence: 99%

Peptide nucleic acids: Advanced tools for biomedical applications

Gupta

Mishra

Puri³

2017

Journal of Biotechnology

143

120

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Peptide Nucleic Acids (PNAs) are the DNA/RNA analogues in which sugar-phosphate backbone is replaced by N-2-aminoethylglycine repeating units. PNA contains neutral backbone hence due to the absence of electrostatic repulsion, its hybridization shows remarkable stability towards complementary oligonucleotides. PNAs are highly resistant to cleavage by chemicals and enzymes due to the substrate specific nature of enzymes and therefore not degraded inside the cells. PNAs are emerging as new tools in the market due to their applications in antisense and antigene therapies by inhibiting translation and transcription respectively. Hence, several methods based on PNAs have been developed for designing various anticancer and antigene drugs, detection of mutations or modulation of PCR reactions. The duplex homopurine sequence of DNA may also be recognized by PNA, forming firm PNA/DNA/PNA triplex through strand invasion with a looped-out DNA strand. PNAs have also been found to replace DNA probes in varied investigative purposes. There are several disadvantages regarding cellular uptake of PNA, so modifications in PNA backbone or covalent coupling with cell penetrating peptides is necessary to improve its delivery inside the cells. In this review, hybridization properties along with potential applications of PNA in the field of diagnostics and pharmaceuticals are elaborated.

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Polyanionic Carboxyethyl Peptide Nucleic Acids (ce-PNAs): Synthesis and DNA Binding

Cited by 16 publications

References 73 publications

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

Advanced Evanescent-Wave Optical Biosensors for the Detection of Nucleic Acids: An Analytic Perspective

Peptide nucleic acids: Advanced tools for biomedical applications

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