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Peptide Nucleic Acids: Synthetic Mimics of DNA | LifeTein Peptide Blog

Peptide nucleic acids (PNAs) are synthetic mimics of DNA. The deoxyribose phosphate backbone of PNAs is replaced by a pseudo-peptide polymer. These specific physicochemical properties are exploited to develop a wide range of powerful biomolecular tools, includ

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Peptide nucleic acids (PNAs) are synthetic mimics of DNA. The deoxyribose phosphate backbone of PNAs is replaced by a pseudo-peptide polymer. These specific physicochemical properties are exploited to develop a wide range of powerful biomolecular tools, including molecular probes, biosensors, and antigene agents. The PNA molecules can routinely be labeled with biotin, azido, cell penetration peptide fragments, or fluorophores such as FITC, Cy3, Cy5, Cy7, Alexa Dyes, and pyrene.

The uncharged synthetic backbone provides PNA with unique hybridization characteristics. It gives higher stability, or a higher thermal melting temperature (Tm) to the PNA–DNA or PNA–RNA duplexes than the natural homo- or heteroduplexes. In addition, the unnatural backbone of PNAs is not degraded by nucleases or proteases.

It was shown that the binding of PNA to complementary DNA can efficiently block transcriptional elongation and inhibit the binding of transcriptional factors. Thus, the PNAs can be used as antisense or antigene therapeutic agents. PNAs can be used as adapters to link peptides, drugs, or molecular tracers to plasmid vectors. One concept is to form the duplexes of PNAs – cell penetration peptides. The duplexes can penetrate into cells and be used in anticancer applications. The nuclear localization signal (NLS) peptide-PNAs duplexes gave a much higher nuclear localization of a coupled nuclear localization signal than did the free oligonucleotide.

The strategy of PNA-directed PCR clamping is used to inhibit the amplification of a specific target. This PNA–DNA complex formed at one of the primer sites effectively blocks the formation of the PCR product. The procedure can be used to detect single base-pair gene variants for mutation screening and gene isolation. The biotinylated short PNA probes can be used as generic capture probes for the purification of nucleic acids via streptavidin beads. Other applications could be solid-phase hybridization, and fluorescence in situ hybridization (PNA-FISH).

PNA-based applications benefit from the unique Physico-chemical properties of PNA molecules, enabling the development of cell penetration peptide-PNA assays in molecular genetics.

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Case Study: Confidential PNA–Peptide Conjugate Featuring Pseudoisocytosine and Click-Ready Handle

To demonstrate the capabilities of our custom PNA–peptide synthesis service, we present a representative structure that illustrates the complexity and flexibility of our platform. Due to client confidentiality, the full sequence cannot be disclosed, but the following anonymized format captures its essential features: H‑PKKKRKVKK‑{TxJTxxJJ}‑linker‑{CxxxTCxxxT}‑x‑K(N₃)‑NH₂ Cell-Penetrating Peptide (CPP): The N-terminal peptide sequence PKKKRKVKK is derived from classical nuclear localization signals (NLS) and cell-penetrating motifs to promote efficient intracellular delivery of the PNA cargo. PNA Segments with Monomer J: {TxJTxxJJ} and {CxxxTCxxxT} represent two PNA domains, with the incorporation of pseudoisocytosine (J) enhancing triplex stability under physiological pH. This design is particularly suited for sequence-specific DNA/RNA targeting, even in mismatch-rich or purine-rich regions. Flexible Linker (e.g., eg1): A short PEG-like spacer connects the two PNA domains to allow conformational flexibility and minimize steric hindrance during hybridization. Click Chemistry Handle: A C-terminal Lys(N₃) provides an azido group for site-specific bio-orthogonal conjugation (e.g., to fluorophores, biotin, or nanocarriers via CuAAC or SPAAC chemistry). This structure highlights our ability to: Synthesize challenging monomers such as J (pseudoisocytosine) Incorporate complex PNA–peptide hybrids Deliver products suitable for gene regulation, antisense studies, or targeted delivery platforms CPP-PNA Examples CPP Sequence Pen RQIKIWFQNRRMKWKK-PNA Tat GRKKRRQRRRPPQ-PNA 47Tat57 GGGGYGRKKRRQRRR-PNA Cationic KKKK-PNA Lys K-PNA-KKK Arg RRRRRRRR-PNA H region AAVALLPAVLLALLA-PNA PTD-4 YARAAARQARA-PNA Tp-10 AGYLLGKINLKALAALAKKIL-PNA SSBP(I) PKKKRKV-PNA C-myc tag EQKLISEEDLNA-PNA Tat-modified RRRQRRKKR-PNA We use essential cookies to make our site work. With your consent, we may also use non-essential cookies to improve user experience and analyze website traffic. You can accept all cookies or continue with essential cookies only. See our Cookie Policy.

Source: lifetein.com ↗

Case Study: Fluorescent PNA with Azido Handle

This case study shows a PNA synthesis with a fluorescent Cyanine Dye Cy5 modification at the N-terminus and an azido group at the C-terminus for downstream click chemistry. Cys(Cy5)-{XXXXXX}-Lys(N3)-NH2, where X represents A, T, G, or C monomers. Fmoc-Lys(N3)-OH was used to introduce a side-chain azido group that remains suitable for selective downstream modification.

Source: lifetein.com ↗
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Peptide Therapy Guide Editorial Team

Editorial team for Peptide Therapy Guide.

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