Independent education resourceInformation here does not replace care from a qualified health professional.
Peptide Therapy GuideClear peptide education

Educational guide

Peptide Nucleic Acids (PNA) Synthesis and Conjugation

Peptide Nucleic Acids (PNA) Synthesis and Conjugation Peptide nucleic acids (PNAs) are synthetic DNA/RNA analogs in which the nucleobases are attached to a neutral polyamide backbone rather than a sugar-phosphate backbone. Because of this structure, PNAs can b

Written by Peptide Therapy Guide Editorial Team
For education only

This guide cannot diagnose a condition or recommend a personal treatment plan. Discuss medical questions with a qualified professional.

Peptide Nucleic Acids (PNA) Synthesis and Conjugation

Peptide nucleic acids (PNAs) are synthetic DNA/RNA analogs in which the nucleobases are attached to a neutral polyamide backbone rather than a sugar-phosphate backbone. Because of this structure, PNAs can bind DNA or RNA targets strongly and sequence-specifically, while offering high resistance to nucleases and proteases.

LifeTein supports both standard PNA oligomer synthesis and more advanced PNA formats, including peptide–PNA conjugates, fluorescently labeled PNAs, click-ready constructs, and modified monomer designs for research, diagnostic, and delivery-related applications.

PNA Service Overview

Core formats

PNA oligomers, labeled PNAs, peptide–PNA conjugates, PNA FISH probes, and advanced functionalized constructs

Typical applications

Antisense studies, antigene strategies, PCR clamping, FISH probes, imaging, biosensors, and targeted delivery research

Available modifications

Fluorophores, quenchers, biotin, click handles, linkers, lipidation, peptide conjugation, and selected custom monomers

Advanced capability

CPP-PNA designs, pseudoisocytosine-containing constructs, dual-domain PNA designs, and click-ready azido/alkyne handles

Project support

Sequence review, solubility guidance, linker suggestions, and design discussion for specialized PNA applications

When to Use PNA

When stronger binding to DNA or RNA is needed than can typically be achieved with standard DNA or RNA analogs

When enzymatic stability is important

For PCR clamping or selective suppression of wild-type amplification

For FISH probes and imaging applications under low-salt or challenging conditions

For antisense, antigene, miRNA inhibition, or duplex invasion strategies

For specialized delivery systems using peptide–PNA conjugates or click-enabled functionalization

For a broader decision guide, see When to Use PNA Instead of DNA or RNA.

Discuss Your PNA Project

You can contact us about sequence design, labels, peptide conjugation, click handles, solubility, or other PNA-specific requirements.

Need a formal quotation? Please use the online quote form below.

PNA Formats and Modifications

LifeTein provides custom PNA oligo design, labeling, and conjugation, including unlabeled PNA oligomers, fluorescently labeled PNAs, peptide–PNA conjugates, and other specialized formats. Available labels and functional groups include fluorophores such as FAM, FITC, Alexa Fluor dyes, ATTO dyes, and cyanine dyes (Cy3, Cy5, Cy7); quenchers such as BHQ and Dabcyl; as well as biotin, maleimide, azide, alkyne handles, lipidation, and other custom modifications.

PNA Design Considerations

PNA lengths of about 10–30 mers are used in many common applications.

PNA melting temperatures are often higher than those of comparable DNA probes.

Longer PNA sequences with high purine content may have reduced water solubility.

Additional lysines or linkers such as AEEA, E linkers, or X linkers can improve solubility.

Strong self-complementarity, hairpin-forming, inverse-repeat, or palindromic designs should generally be avoided.

Selected PNA Products and Probe Formats

For stocked or semi-standard examples, see PNA probes, inhibitors, and selected products.

PMP01-25

Peptide nucleic acid (PNA) PMP01-25: {GGCAAGTCTTCTTCGGA}-NH2

$350, 50 nmol, In Stock

APP01-25

Peptide nucleic acid (PNA) APP01-25: {GGCTCAACTCTGGACAG}-NH2

EcoPNA1169

Peptide nucleic acid (PNA) EcoPNA1169: Biotin-{CAACACACAGTGTC}

LT8195

(KFF)3K-PNA: KFFKFFKFFK-CTCATACTCT

$450, 25 nmol, In Stock

Peptide-Conjugated Antisense PNA

(RXR)4XB-{O}-{gccatttgac}

$450, 50 nmol, In Stock

PNA FISH Probe Examples

TelC telomere probe

CCCTAACCCTAACCCTAA; reverse complementary sequence: TTAGGGTTAGGGTTAGGG

TelG telomere probe

TTAGGGTTAGGGTTAGGG; reverse complementary sequence: CCCTAACCCTAACCCTAA

Pan-centromere CENPB probe

ATTCGTTGGAAACGGGA; reverse complementary sequence: TCCCGTTTCCAACGAAT

Human-only pan-centromere CENT probe

AAACTAGACAGAAGCATT; reverse complementary sequence: AATGCTTCTGTCTAGTTT

PNA Applications

Microarrays and biosensors

PCR clamping and artificial restriction strategies

Imaging probes and FISH

Antisense and antigene studies

miRNA inhibitors

Double-strand DNA invasion and capture

PNA-assisted DNAzyme and PNAzyme concepts

Lipid nanoparticle and delivery-related work

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

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

To illustrate the complexity of our PNA platform, the following anonymized construct represents a confidential PNA–peptide conjugate format:

H-PKKKRKVKK-{TxJTxxJJ}-linker-{CxxxTCxxxT}-x-K(N₃)-NH₂

Key features of this construct

A cell-penetrating peptide sequence derived from nuclear localization or delivery motifs

PNA domains containing pseudoisocytosine (J) to improve triplex stability

A flexible linker to reduce steric constraints during hybridization

A click-ready Lys(N₃) handle for site-specific downstream conjugation

Application relevance

Synthesis of difficult monomers such as J (pseudoisocytosine)

Construction of advanced peptide–PNA hybrids

Formats suitable for gene regulation, antisense studies, and targeted delivery research

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.

Related PNA Resources

When to Use PNA Instead of DNA or RNA

Custom PNA Oligo Design, Labeling, and Conjugation

PNA Probes, Inhibitors, and Selected Products

PNA-Assisted DNAzyme Systems and PNAzyme Concepts

Need help planning a PNA project?

We are happy to review standard PNA oligomers, peptide–PNA conjugates, fluorescent PNA probes, CPP-PNA constructs, and other advanced formats.

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.

Connected reading

Helpful context for this guide

Source-derived material selected through this article’s indexed topics.

Research context

Read sources and limitations before applying a claim.

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 ↗
P

About the author

Peptide Therapy Guide Editorial Team

Editorial team for Peptide Therapy Guide.

View all articles →