Peptide–PNA Conjugation Services

Peptide–PNA conjugates are chemically defined oligonucleotide–peptide constructs in which a peptide is covalently linked to a peptide nucleic acid (PNA) oligomer. PNA is a synthetic DNA mimic with a neutral peptide-like backbone, offering strong and specific hybridization to complementary DNA or RNA while enabling diverse chemical modification strategies.

Bio-Synthesis provides peptide–PNA conjugation services as an end-to-end offering, including in-house PNA synthesis, peptide synthesis, and site-defined conjugation using chemoselective linker strategies. This integrated approach supports the generation of single, well-defined peptide–PNA conjugates suitable for reproducible research and development workflows.

Conjugation routes are selected based on handle placement, linker stability, and downstream analytical requirements, and may be performed via copper-free click chemistry, thiol-based coupling, or amide bond formation. Each conjugate is purified and analytically verified using mass spectrometry and chromatographic and/or capillary gel electrophoresis methods, with documentation aligned to the intended program stage.

Peptide–PNA conjugation services are part of our broader oligonucleotide–peptide conjugation capabilities, supporting related DNA, RNA, and antisense platforms.

Related services: Oligonucleotide Conjugation, Peptide Modifications, Click Chemistry Peptides.

• PNA backbone: neutral, peptide-like scaffold supporting strong, specific base pairing with complementary DNA/RNA
• Stability concept: PNA designs are often explored for nuclease resistance and defined hybridization behavior
• Conjugation value: peptides can provide targeting or CPP concepts to support cellular association while keeping a single, defined construct
• Reproducibility: defined 1:1 conjugates enable clear structure–property comparisons across variants

Note: performance depends on sequence, model system, and design context; we focus on producing well-defined materials and documentation.

Standard PNA

• Custom sequences
• Terminal handles for conjugation
• Optional labels (program-dependent)

Functionalized PNA

• 5′/3′ handle placement (design-dependent)
• Azide/alkyne, thiol, amine, DBCO/BCN options
• Spacer/PEG tuning

Specialty designs

• Chimera-like constructs (program-dependent)
• Multivalent/branched architectures (program-dependent)
• Compatibility review before build

CPP prototypes

Often used as starting points to increase cellular association (context-dependent).

• TAT-derived peptides
• Penetratin-derived peptides
• Oligo-arginine (R8 / R9)
• Transportan-related designs

Targeting ligands

Used to explore receptor-mediated uptake concepts (selection depends on model and goals).

• RGD / iRGD motifs
• Receptor-binding peptides (program-dependent)
• Affinity/assay tags

Architectures

Options when programs require additional features.

• Branched peptides (site-defined)
• Spacers/PEG for sterics & solubility
• Dual-handle constructs (program-dependent)

Copper-free click (DBCO/BCN)

A common default for chemoselectivity and reproducible conversion.

• Azide–DBCO / azide–BCN
• Site-defined attachment
• Clean byproduct profile

Thiol–maleimide

Fast coupling using terminal thiols and maleimide handles.

• Useful for feasibility builds
• Handle planning minimizes mixtures
• Stabilized designs (program-dependent)

Amide coupling

Activated ester routes when click handles are constrained.

• Amine–carboxyl coupling
• Protected-handle strategies
• Careful control to limit heterogeneity

Cleavable linkers

Selected when intracellular release concepts are required (program-dependent).

• Disulfide (reducible)
• Other cleavable designs (program-dependent)

Non-cleavable linkers

Preferred when stable linkage is the priority.

• Stable thioether or triazole linkages
• Construct stability for tracking/controls

Design inputs we review

• PNA: sequence/length, handle placement, polarity/solubility constraints
• Peptide: attachment site, net charge, hydrophobicity; optional branching
• Linker: stable vs cleavable; spacer length (PEG/alkyl) for sterics
• Purification: route selected to separate PNA, peptide, and conjugate cleanly
• Controls: optional PNA-only/peptide-only or matched variants

Mechanism note (CMC-safe)

Peptides used in PNA conjugates may support cellular association and uptake through multiple pathways (including receptor-mediated endocytosis for targeted ligands and other uptake routes for cationic CPPs). Design decisions (net charge, hydrophobicity, and linker architecture) are made to match the intended uptake concept while balancing stability, solubility, and analytical clarity.

• PNA + peptide design review – confirm sequences, handle placement, and linker strategy.
• PNA synthesis – build and deprotect PNA with planned functional handles.
• Peptide synthesis – prepare peptide with a single defined attachment site/handle.
• Conjugation + purification – chemoselective coupling followed by separation of conjugate from components.
• Analytical QC + release – identity and purity verification with documentation aligned to intended use.

Identity

• Mass spectrometry confirmation
• Conjugation verification (method-appropriate)

Purity

• Chromatography and/or capillary gel electrophoresis
• Separation from unreacted components

Documentation

• COA aligned to program stage
• Traceable documentation package (program-dependent)