Year: 2026
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Peptide nucleic acid (PNA) is a synthetic DNA analogue characterized by exceptional biostability and strong hybridization affinity toward complementary DNA and RNA. However, its inherently low membrane permeability hampers its biomedical applicability. N -Methylation of guanine and adenine PNA monomers produces a positively charged nucleobase, which suppresses the formation of self-duplexes while improving DNA affinity through electrostatic interactions. To overcome the cellular delivery limitations of PNA, we designed and synthesized a 16-mer, nontargeted model PNA incorporating 4, 6, or 8 positively charged purines (G + and A + ). As comparative controls, the corresponding unmodified PNA was conjugated to a short cell-penetrating peptide (CPP) containing 4, 6, or 8 d -lysine residues. All constructs were labeled with Rhodamine B to enable quantitative cellular uptake analysis. Flow cytometry and confocal microscopy in OVCAR-8 ovarian cancer cells revealed that the PNA incorporating six positively charged purines (MCP6, multiple charged purines with an overall 6 positive charges) exhibited markedly enhanced cellular internalization compared to both the other MCP-PNAs and the CPP-PNA controls. MCP-PNAs showed no noticeable signs of cell toxicity, and their binding affinities (thermal melting profiles) were comparable to CPP-PNAs. In addition, MCP-PNAs well discriminated single mismatches in RNA, similarly to CPP-PNAs. Overall, this strategy provides a simple and effective approach for generating inherently cell-permeable PNAs.
Source: ACS Polymers Au
Authors: Salam Maree, Eylon Yavin
Institution: Hebrew University of Jerusalem
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
Award: G5723847667
OpenAlex ID: W7155089305