Pyrrolidinyl peptide nucleic acid with α/β-peptide backbone

Vilaivan, Chotima; Srisuwannaket, Choladda; Ananthanawat, Cheeraporn; Suparpprom, Chaturong; Kawakami, Junji; Yamaguchi, Yoshie; Tanaka, Yukinori; Vilaivan, Tirayut

doi:10.4161/adna.2.2.16340

Cited by 47 publications

(32 citation statements)

References 55 publications

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“…1) exhibits significant features. 11 This feature stands in contrast to many other PNA scaffolds that bind to themselves equally or even better than to naturally occurring nucleic acids. As a result of this structural design, acpcPNA forms stable hybrids with complementary DNA but significantly less stable hybrids with complementary RNA.…”

Section: Introductionmentioning

confidence: 98%

“…[1][2][3][4] The attempt to increase affinity and, more importantly, sequence selectivity of PNA by incorporation of cyclic derivatives in the peptide backbone failed in many cases since the nucleic acid hybridization properties are deteriorated. [10][11][12][13] The recognition and binding to DNA shows high sequence selectivity and does not tolerate single base mismatches. 1) exhibits significant features.…”

Section: Introductionmentioning

confidence: 99%

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Strand displacement and duplex invasion into double-stranded DNA by pyrrolidinyl peptide nucleic acids

2015

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The so-called acpcPNA system bears a peptide backbone consisting of 4'-substituted proline units with (2'R,4'R) configuration in an alternating combination with (2S)-amino-cyclopentane-(1S)-carboxylic acids. acpcPNA forms exceptionally stable hybrids with complementary DNA. We demonstrate herein (i) strand displacements by single-stranded DNA from acpcPNA-DNA hybrids, and by acpcPNA strands from DNA duplexes, and (ii) strand invasions by acpcPNA into double-stranded DNA. These processes were studied in vitro using synthetic oligonucleotides and by means of our concept of wavelength-shifting fluorescent nucleic acid probes, including fluorescence lifetime measurements that allow quantifying energy transfer efficiencies. The strand displacements of preannealed 14mer acpcPNA-7mer DNA hybrids consecutively by 10mer and 14mer DNA strands occur with rather slow kinetics but yield high fluorescence color ratios (blue : yellow or blue : red), fluorescence intensity enhancements, and energy transfer efficiencies. Furthermore, 14mer acpcPNA strands are able to invade into 30mer double-stranded DNA, remarkably with quantitative efficiency in all studied cases. These processes can also be quantified by means of fluorescence. This remarkable behavior corroborates the extraordinary versatile properties of acpcPNA. In contrast to conventional PNA systems which require 3 or more equivalents PNA, only 1.5 equivalents acpcPNA are sufficient to get efficient double duplex invasion. Invasions also take place even in the presence of 250 mM NaCl which represents an ionic strength nearly twice as high as the physiological ion concentration. These remarkable results corroborate the extraordinary properties of acpcPNA, and thus acpcPNA represents an eligible tool for biological analytics and antigene applications.

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Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Strand displacement and duplex invasion into double-stranded DNA by pyrrolidinyl peptide nucleic acids

2015

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“…The 3-aminopyrrolidine-4-carboxylic acid (apc) modified acpcPNA was manually synthesized at a 1.5 µmol scale on Tentagel S-RAM resin (Fluka, 0.24 mmol/g) from the four Fmoc-protected pyrrolidinyl PNA monomers (A Bz , T, C Bz , G Ibu ) and spacers [Fmoc-(1 S ,2 S )-2-aminocycolpentanecarboxylic acid or (3 R ,4 S )-3-(Fmoc-amino)-1-trifluoroacetylpyrrolidine-4-carboxylic acid] [ 43 ] according to the previously published protocol [ 26 – 27 31 ]. Lysine was included at both C- and N-termini to improve the water solubility.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

Yotapan¹,

Charoenpakdee²,

Wathanathavorn³

et al. 2014

Beilstein J. Org. Chem.

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SummaryDNA or its analogues with an environment-sensitive fluorescent label are potentially useful as a probe for studying the structure and dynamics of nucleic acids. In this work, pyrrolidinyl peptide nucleic acid (acpcPNA) was labeled at its backbone with Nile red, a solvatochromic benzophenoxazine dye, by means of click chemistry. The optical properties of the Nile red-labeled acpcPNA were investigated by UV–vis and fluorescence spectroscopy in the absence and in the presence of DNA. In contrast to the usual quenching observed in Nile red-labeled DNA, the hybridization with DNA resulted in blue shifting and an enhanced fluorescence regardless of the neighboring bases. More pronounced blue shifts and fluorescence enhancements were observed when the DNA target carried a base insertion in close proximity to the Nile red label. The results indicate that the Nile red label is located in a more hydrophobic environment in acpcPNA–DNA duplexes than in the single-stranded acpcPNA. The different fluorescence properties of the acpcPNA hybrids of complementary DNA and DNA carrying a base insertion are suggestive of different interactions between the Nile red label and the duplexes.

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“…The thermal stability of the acp-cPNA and DNA hybrid is more stable than the acpcPNA and RNA hybrid having the same sequence. The acpcPNA does not show the potential to form self-pairing hybrids; hence, it is used as antigene agents (Vilaivan et al, 2011). The modification of ring size changed the rigidity and also the torsional angle of NH-C2-C1-CO which is an integral part of the backbone of the PNA system and affects the hybridization properties of PNA.…”

Section: Das and Pradhanmentioning

confidence: 99%

“…Mostly, the higher affinities are obtained with the retention of base-pairing specificities as the mismatched complexes were found to be more destabilizing than the unmodified PNA. The study of hybridization properties of pyrrolidinyl PNA showed that the PNA with carboxylic 2-aminocyclopentane carboxylic acid (acpc) spacer possesses four diastereomers and among these only the pyrrolidinyl PNA carrying a (2R,4R)pyrrolidinyl (1S,2S) backbone forms a stable hybrid with the DNA as the T m value was found to be more than 85°C (Vilaivan et al, 2011). Similarly, Pyrrolidinyl PNA having acbc spacer the (1S,2S)-2aminocyclobutane carboxylic acid [(1S,2S)-acbc] and (3R)-aminopyrrolidine-(4S)-carboxylic acid [(3R,4S)-apc] (Reenabthue et al, 2011) formed a stable hybrid complex with DNA.…”

Section: Hybridization Propertiesmentioning

confidence: 99%

Evolution of peptide nucleic acid with modifications of its backbone and application in biotechnology

Das

Pradhan

2020

Chem Biol Drug Des

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Peptide nucleic acids (PNAs) are getting prodigious interest currently in the biomedical and diagnostic field as an extremely powerful tool because of their potentiality to hybridize with natural nucleic acids. Although PNA has strong affinity and sequence specificity to DNA/RNA, there is a considerable ongoing effort to further enhance their special chemical and biological properties for potential application in numerous fields, notably in the field of therapeutics. The toolbox for backbone modified PNAs synthesis has been extended substantially in recent decades, providing a more efficient synthesis of peptides with numerous scaffolds and modifications. This paper reviews the various strategies that have been developed so far for the modification of the PNA backbone, challenging the search for new PNA systems with improved chemical and physical properties lacking in the original aegPNA backbone. The various practical issues and limitations of different PNA systems are also summarized. The focus of this review is on the evolution of PNA by its backbone modification to improve the cellular uptake, sequence specificity, and compatibility of PNA to bind to DNA/RNA. Finally, an insight was also gained into major applications of backbone modified PNAs for the development of biosensors.

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Pyrrolidinyl peptide nucleic acid with α/β-peptide backbone

Cited by 47 publications

References 55 publications

Strand displacement and duplex invasion into double-stranded DNA by pyrrolidinyl peptide nucleic acids

Strand displacement and duplex invasion into double-stranded DNA by pyrrolidinyl peptide nucleic acids

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

Evolution of peptide nucleic acid with modifications of its backbone and application in biotechnology

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