Molecular Computing by PNA

Totsingan, Filbert; Marchelli, Rosangela; Corradini, Roberto

doi:10.4161/adna.2.1.15459

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…PNA Oligomer Synthesis : The solid‐phase synthesis of PNA sequence H‐(AEEA) 2 ‐CTTTCCTTCACTGTT‐NH 2 was performed as reported in ref. and that of labeled PNA sequence H‐TAMRA‐(D‐Lys)‐GTAGATGA‐NH 2 was carried out as reported elsewhere …”

Section: Methodsmentioning

confidence: 99%

Intracellular Delivery of Peptide Nucleic Acid and Organic Molecules Using Zeolite‐L Nanocrystals

Bertucci

Lülf

Septiadi

et al. 2014

Adv Healthcare Materials

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The design and synthesis of smart nanomaterials can provide interesting potential applications for biomedical purposes from bioimaging to drug delivery. Manufacturing multifunctional systems in a way to carry bioactive molecules, like peptide nucleic acids able to recognize specific targets in living cells, represents an achievement towards the development of highly selective tools for both diagnosis and therapeutics. This work describes a very first example of the use of zeolite nanocrystals as multifunctional nanocarriers to deliver simultaneously PNA and organic molecules into living cells. Zeolite-L nanocrystals are functionalized by covalently attaching the PNA probes onto the surface, while the channel system is filled with fluorescent guest molecules. The cellular uptake of the PNA/Zeolite-L hybrid material is then significantly increased by coating the whole system with a thin layer of biodegradable poly-L-lysine. The delivery of DAPI as a model drug molecule, inserted into the zeolite pores, is also demonstrated to occur in the cells, proving the multifunctional ability of the system. Using this zeolite nanosystem carrying PNA probes designed to target specific RNA sequences of interest in living cells could open new possibilities for theranostic and gene therapy applications.

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Section: Methodsmentioning

confidence: 99%

Intracellular Delivery of Peptide Nucleic Acid and Organic Molecules Using Zeolite‐L Nanocrystals

Bertucci

Lülf

Septiadi

et al. 2014

Adv Healthcare Materials

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“…Compared to dsDNA, shorter PNA:PNA duplexes are exceptionally stable. For instance, four distinct 8-mer PNA:PNA duplexes displayed notably high T m s in the 52–55 °C range, while dsDNA with the same oligonucleotide sequences had about 40 °C lower predicted T m s . In addition, PNAs are superior in the recognition of single-base mutations.…”

Section: Resultsmentioning

confidence: 99%

Shorter Peptide Nucleic Acid Probes Improve Affibody-Mediated Peptide Nucleic Acid-Based Pretargeting

Westerlund,

Oroujeni,

Gestin

et al. 2024

ACS Pharmacol. Transl. Sci.

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Affibody-mediated PNA-based pretargeting shows promise for HER2-expressing tumor radiotherapy. In our recent study, a 15-mer Z HER2:342 -HP15 affibody-PNA conjugate, in combination with a shorter 9-mer [ 177 Lu]Lu-HP16 effector probe, emerged as the most effective pretargeting strategy. It offered a superior tumor-to-kidney uptake ratio and more efficient tumor targeting compared to longer radiolabeled effector probes containing 12 or 15 complementary PNA bases. To enhance the production efficiency of our pretargeting system, we here introduce even shorter 6-, 7-, and 8-mer secondary probes, designated as HP19, HP21, and HP20, respectively. We also explore the replacement of the original 15-mer Z-HP15 primary probe with shorter 12-mer Z-HP12 and 9-mer Z-HP9 alternatives. This extended panel of shorter PNA-based probes was synthesized using automated microwave-assisted methods and biophysically screened in vitro to identify shorter probe combinations with the most effective binding properties. In a mouse xenograft model, we evaluated the biodistribution of these probes, comparing them to the Z-HP15: [ 177 Lu]Lu-HP16 combination. Tumor-to-kidney ratios at 4 and 144 h postinjection of the secondary probe showed no significant differences among the Z-HP9:[ 177 Lu]Lu-HP16, Z-HP9:[ 177 Lu]Lu-HP20, and the Z-HP15:[ 177 Lu]Lu-HP16 pairs. Importantly, tumor uptake significantly exceeded, by several hundred-fold, that of most normal tissues, with kidney uptake being the critical organ for radiation therapy. This suggests that using a shorter 9-mer primary probe, Z-HP9, in combination with 9-mer HP16 or 8-mer HP20 secondary probes effectively targets tumors while minimizing the dose-limiting kidney uptake of radionuclide. In conclusion, the Z-HP9:HP16 and Z-HP9:HP20 probe combinations offer good prospects for both cost-effective production and efficient in vivo pretargeting of HER2-expressing tumors.

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“…Peptide nucleic acids are widely used in DNA recognition for their unique properties, such as high affinity, high sequence selectivity, and high stability to chemical or enzymatic treatments. In recent years, these artificial DNA mimics have also found attractive applications in nanotechnology as programmable helical structures with different helical pitch and increased stability towards chemical and enzymatic degradation, as tools in molecular computing, and as new self‐assembled materials for optical and optoelectronic applications . One of the key features of PNA is the possibility to form homo‐duplexes, where the helix handedness can be controlled by insertion of suitable chiral centers, so that either right‐ or left‐handed helices can be obtained .…”

Section: Methodsmentioning

confidence: 99%

Structural Studies on Porphyrin–PNA Conjugates in Parallel PNA:PNA Duplexes: Effect of Stacking Interactions on Helicity

et al. 2015

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Parallel PNA:PNA duplexes were synthesized and conjugated with meso-tris(pyridyl)phenylporphyrin carboxylic acid at the N-terminus. The introduction of one porphyrin unit was shown to affect slightly the stability of the PNA:PNA parallel duplex, whereas the presence of two porphyrin units at the same end resulted in a dramatic increase of the melting temperature, accompanied by hysteresis between melting and cooling curves. The circular dichroism (CD) profile of the Soret band and fluorescence quenching strongly support the occurrence of a face-to-face interaction between the two porphyrin units. Introduction of a L-lysine residue at the C-terminal of one strand of the parallel duplex induced a left-handed helical structure in the PNA:PNA duplex if the latter contains only one or no porphyrin moiety. The left-handed helicity was revealed by nucleobase CD profile at 240-280 nm and by the induced-CD observed in the presence of the DiSC2 (5) cyanine dye at ~500-550 nm. Surprisingly, the presence of two porphyrin units led to the disappearance of the nucleobase CD signal and the absence of CD exciton coupling within the Soret band region. In addition, a dramatic decrease of induced CD of DiSC2 (5) was observed. These results are in agreement with a model where the porphyrin-porphyrin interactions cause partial loss of chirality of the PNA:PNA parallel duplex, forcing it to adopt a ladder-like conformation.

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Molecular Computing by PNA

Cited by 8 publications

References 38 publications

Intracellular Delivery of Peptide Nucleic Acid and Organic Molecules Using Zeolite‐L Nanocrystals

Intracellular Delivery of Peptide Nucleic Acid and Organic Molecules Using Zeolite‐L Nanocrystals

Shorter Peptide Nucleic Acid Probes Improve Affibody-Mediated Peptide Nucleic Acid-Based Pretargeting

Structural Studies on Porphyrin–PNA Conjugates in Parallel PNA:PNA Duplexes: Effect of Stacking Interactions on Helicity

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