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Updated: Jun 16, 2026
09:04
Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
Multiple Charged Purine (MCP) PNA as a Simple Mode for Cellular Uptake.
1The Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, The Hebrew University of Jerusalem, Hadassah Ein-Kerem, Jerusalem 9112102, Israel.
ACS Polymers Au
|June 15, 2026
Summary
Modified peptide nucleic acids (PNAs) with positively charged purines show enhanced cellular uptake without toxicity. This breakthrough improves PNA delivery for biomedical applications.
Area of Science:
- Biochemistry
- Molecular Biology
- Biotechnology
Background:
- Peptide nucleic acid (PNA) is a synthetic DNA analog with high stability and binding affinity.
- Low membrane permeability limits PNA's biomedical use.
- Modifying PNA monomers with N-methylation creates positively charged bases, enhancing DNA affinity and preventing self-duplex formation.
Purpose of the Study:
- To develop inherently cell-permeable PNAs by incorporating positively charged purines.
- To evaluate the cellular uptake, toxicity, and binding characteristics of these modified PNAs.
- To compare the performance of modified PNAs with PNA-cell-penetrating peptide conjugates.
Main Methods:
- Synthesized 16-mer PNAs with 4, 6, or 8 positively charged purines (MCP-PNAs).
- Prepared control PNAs conjugated to cell-penetrating peptides (CPP-PNAs) with varying d-lysine residues.
- Quantified cellular uptake using Rhodamine B labeling, flow cytometry, and confocal microscopy in OVCAR-8 cells.
Main Results:
- The PNA with six positively charged purines (MCP6) demonstrated significantly higher cellular internalization than other MCP-PNAs and CPP-PNA controls.
- MCP-PNAs exhibited no significant cytotoxicity.
- MCP-PNAs showed comparable binding affinities and RNA mismatch discrimination to CPP-PNAs.
Conclusions:
- Incorporating positively charged purines is an effective strategy to enhance PNA cellular permeability.
- This approach offers a simple and efficient method for creating cell-permeable PNAs for potential biomedical applications.
- MCP-PNAs represent a promising class of molecules for therapeutic and diagnostic development.
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