Peptide–ASO Conjugation Services

Site-defined peptide–antisense oligonucleotide conjugates with development-aware purification and analytics.

Chemically defined constructs designed to support uptake, targeting, and intracellular delivery for antisense workflows across modified DNA/RNA, PS gapmers, and high-affinity bases (LNA/BNA).

Modified DNA/RNA PS gapmers LNA / BNA Optional lipid modification Copper-free click (DBCO/BCN) Cleavable & non-cleavable linkers

Overview

What is peptide–ASO conjugation?

Peptide–ASO conjugation is the site-defined covalent attachment of a peptide to an antisense oligonucleotide (ASO) to create a chemically defined construct. This approach is designed to support cellular uptake, tissue targeting, and intracellular delivery while maintaining ASO integrity and functional antisense activity.

Peptide–ASO conjugates are also referred to as ASO–peptide conjugates or peptide–oligonucleotide conjugates, depending on orientation and application context.

Related services: Peptide Modifications, Peptide Bioconjugation, Click Chemistry Peptides, Cleavable Linker Peptides.

Why peptide–ASO conjugates?

  • Defined 1:1 stoichiometry supporting reproducible manufacturing and interpretation
  • Reduced batch-to-batch variability compared with electrostatic complexation
  • Clear structure–activity relationships to support rational optimization
  • Modular architecture enabling controlled targeting, uptake, and endosomal escape
  • Well-aligned with translational development and regulatory expectations

In contrast to lipid nanoparticle (LNP) formulations, peptide–ASO conjugates offer a chemically defined, single-component construct that simplifies characterization, reproducibility, and early-stage development workflows.

Supported ASO types and base chemistries

Modified DNA / RNA

Common antisense formats, including mixed DNA/RNA designs, can be supported with appropriate handles and linkers.

  • Modified DNA ASOs
  • Modified RNA ASOs
  • Mixed DNA/RNA designs
PS (phosphorothioate) & gapmers

Widely used for RNase H mechanisms; conjugation strategy is selected to preserve intended function.

  • PS backbones
  • Gapmer architectures
  • Steric-blocking ASOs (case-specific)
High-affinity bases

Supports conformationally constrained bases that improve binding affinity and stability.

  • LNA (Locked Nucleic Acid)
  • BNA (Bridged Nucleic Acid)
  • Other constrained base analogs (project-dependent)
Note on compatibility

Conjugation feasibility depends on the available functional handle (e.g., thiol, amine, azide/alkyne) and the desired linker strategy. If you’re unsure, send the ASO design and constraints—we’ll recommend a practical handle + linker plan.

Lipid-modified ASOs prior to peptide conjugation

ASO lipid modification (pre-conjugation)

In addition to direct peptide–ASO conjugation, Bio-Synthesis can introduce lipid motifs as an ASO modification prior to peptide attachment to support dual-modality designs (lipid + peptide).

  • Fatty acid motifs (e.g., palmitic, stearic)
  • Sterol-type motifs (e.g., cholesterol derivatives)
  • Other hydrophobic motifs (project-dependent)
When it’s used

Lipid modification may be used to tune circulation behavior, protein binding, or membrane interaction prior to peptide delivery.

  • Dual-modality delivery constructs
  • Comparability studies (lipid vs peptide vs dual)
  • Early-stage screening of delivery architectures

Linker & conjugation chemistry

Copper-free click (DBCO/BCN)

A common default for chemoselectivity and reproducible conversion.

  • Azide–DBCO / azide–BCN
  • High selectivity and reproducible conversions
  • Operationally simple cleanup
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 is required (project-dependent).

  • Disulfide (reducible)
  • Other cleavable designs (case-specific)
Non-cleavable linkers

Preferred when stable linkage is the priority.

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

Reaction conditions and workup are selected to minimize oligonucleotide degradation and preserve construct homogeneity.

Workflow / procedure

Typical workflow for peptide–PNA conjugate synthesis, purification, and analytical control
Typical workflow for peptide–ASO conjugate synthesis, purification, and analytical control.
  • ASO design & modification map – Confirm base chemistry (DNA/RNA/LNA/BNA), backbone, and desired modification pattern.
  • Handle installation – Introduce compatible functional handles (thiol, amine, azide/alkyne, DBCO/BCN) at the chosen position.
  • Peptide–ASO conjugation – Perform chemoselective coupling with controlled reaction conditions.
  • Purification – Isolate the desired conjugate and remove unreacted components (e.g., HPLC/SEC).
  • Analytical QC + delivery – Confirm identity/conjugation and provide QC documentation aligned to the intended use.

This workflow supports feasibility studies through translational programs by aligning chemistry, purification, and analytics to the stage of development.

Development considerations
  • Early selection of attachment site and linker chemistry simplifies downstream characterization and comparability.
  • Chemically defined conjugates support clearer structure–activity relationships than multicomponent delivery systems.
  • Cleaveable versus non-cleavable linkers should be chosen based on the need for intracellular release versus construct stability.
  • Analytical strategies may evolve as programs progress from feasibility to translational studies.

Bio-Synthesis can align conjugation strategy, purification, and analytical depth to the intended stage of development.

QC & typical deliverables

Standard QC
  • Purity assessment (chromatography-based)
  • Identity and conjugation confirmation using mass-based and orthogonal methods where applicable
  • COA + method summary
Optional controls
  • ASO-only control
  • Peptide-only control
  • Matched design variants (linker/handle comparisons)
Aligned to intended use

Analytical depth and documentation can be aligned to feasibility, preclinical, or translational workflows.

FAQ

What ASO chemistries do you support?

We support common antisense formats including modified DNA/RNA and PS gapmer designs, as well as high-affinity bases such as LNA and BNA. Feasibility depends on handle placement and linker strategy.

Can you lipid-modify an ASO before peptide conjugation?

Yes. We can introduce lipid motifs as an ASO modification prior to peptide attachment to support dual-modality (lipid + peptide) constructs when appropriate.

Which linker chemistry should I choose?

Copper-free click is a common default for RNA compatibility and site specificity. Thiol–maleimide or amide coupling may be suitable depending on available handles. Cleavable or non-cleavable linkers can be selected based on stability and release requirements.

What do you need for a quote?

Send ASO sequence and modification pattern (DNA/RNA/PS/LNA/BNA), any lipid modification request, peptide sequence and handle/attachment preference, preferred linker chemistry (or ask us to recommend), plus target quantity and purity.

Contact & quote request

For the fastest quote, send your ASO sequence and modification pattern (DNA/RNA/PS/LNA/BNA), any lipid modification request, peptide sequence/handle, preferred attachment site (or constraints), linker preference (or “recommend”), and quantity/purity targets.

Fastest path
Fast quote checklist
  • ASO sequence + modification pattern
  • Backbone details (e.g., PS) and architecture (e.g., gapmer)
  • LNA/BNA content (if applicable)
  • Lipid modification request (if applicable)
  • Peptide sequence + desired handle/attachment preference
  • Linker preference (or “recommend”) + cleavable vs stable
  • Quantity (mg) + purity target + intended use

Not sure which route is safest? Send sequences and constraints—we’ll propose a handle + linker plan aligned to your ASO chemistry.

Why Choose Bio-Synthesis

Trusted by biotech leaders worldwide for over 40+ years of delivering high quality, fast and scalable synthetic biology solutions.