Peptide–DNA Conjugation Services

Site-defined peptide–ssDNA & peptide-dsDNA conjugates with development-aware purification and analytics.

Chemically defined peptide–ssDNA and peptide-dsDNA conjugates for research and delivery concepts

Overview

Peptide–DNA conjugates (including peptide–ssDNA and peptide–dsDNA conjugates) are chemically defined constructs in which a peptide is covalently linked to single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) to support targeting, delivery concepts, or functional assays while preserving DNA hybridization properties.

Bio-Synthesis provides peptide–DNA conjugation services supporting ssDNA, dsDNA, and modified DNA formats with site-defined peptide attachment, practical conjugation routes (solid-phase or solution-phase), purification, and fit-for-purpose QC documentation. This service complements our broader oligonucleotide conjugation capabilities.

Bio-Synthesis offers custom DNA–peptide conjugates (also called oligonucleotide–peptide conjugates, OPCs) using selective cross-linking chemistries and site-defined functional handles to meet program requirements for attachment site control, stability, and purification. In many research settings, peptide carriers (including CPP or targeting concepts) are explored to support cellular association and uptake, while keeping a single, chemically defined construct suitable for reproducible characterization.

As specialists in bioconjugation, we support multiple coupling strategies including (but not limited to) click chemistry and native ligation-based approaches, selected based on DNA format, handle placement, and compatibility with downstream analytics. Each conjugate is monitored across the production cycle under our quality systems, with identity characterization by mass spectrometry and purity assessment using high-throughput capillary gel electrophoresis and/or chromatography as appropriate.

Bio-Synthesis DNA–peptide conjugate services
  • Wide selection of synthesis scales, modifications, treatments, and purification options
  • Oligo–peptide conjugates across multiple formats (DNA conjugates, RNA conjugates, siRNA conjugates, and BNA conjugates)
  • Fully traceable documentation system (program-aligned)
Defined 1:1 constructs Stable or cleavable linkers Solid-phase or solution-phase Program-aligned QC

Scope note: This page describes synthesis, conjugation, purification, and analytical qualification. It does not report biological efficacy or clinical outcomes; delivery performance is context-dependent.

Related services: Peptide Modifications, Peptide Bioconjugation, Click Chemistry Peptides, Lipid / Fatty Acid Conjugation.

Why peptide–DNA conjugates?

  • Defined 1:1 stoichiometry supporting reproducible characterization and comparability
  • Reduced variability versus electrostatic complexation strategies
  • Modular architecture for targeting ligands, CPP concepts, and assay constructs
  • Clear structure–property relationships to support rational optimization
  • Compatibility with program-aligned purification and analytical documentation

DNA formats we support

ssDNA (peptide–ssDNA conjugates)

Single-stranded DNA constructs with defined terminal handles (5′/3′) and optional internal handles (program-dependent).

  • 5′ or 3′ functional handles
  • Short to moderate-length ssDNA
  • Optional labels/handles (design-dependent)
dsDNA (peptide–dsDNA conjugates)

Typically assembled from annealed strands; peptide attachment can be planned on one strand or at defined termini.

  • Annealed duplex constructs
  • Defined attachment placement
  • Program-dependent size range
Modified DNA

Selected modified DNA designs can be evaluated when compatible handles and purification strategy are defined.

  • Phosphorothioate DNA (PS)
  • Chimera designs (design-dependent)
  • Other specialty modifications (program-dependent)
Compatibility note

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 DNA design and constraints—we’ll recommend a practical handle + linker plan. We can support both peptide–ssDNA and peptide–dsDNA build strategies when the handle placement and purification plan are defined.

Common peptide options

CPP prototypes

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

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

Selected to bias uptake via receptor-mediated pathways (selection depends on model and goals).

  • RGD / iRGD motifs
  • Other receptor-binding peptides (program-dependent)
  • Affinity tags for assay constructs
Architectures

Optional designs when the program requires multivalency or additional functional features.

  • Branched peptides (site-defined)
  • PEG/spacer tuning for sterics
  • Dual-handle constructs (program-dependent)
Selection note (CMC-friendly)

We can synthesize the peptide you specify or recommend a practical starting set based on attachment site constraints, charge/solubility limits, and the desired linker chemistry. Final biological performance depends on sequence, model system, and dosing context.

Linker & conjugation chemistry

Copper-free click (DBCO/BCN)

A common default for oligonucleotide compatibility and site specificity.

  • Azide–DBCO / azide–BCN
  • High selectivity and reproducible conversions
  • Straightforward workup and cleanup
Thiol–maleimide

Fast coupling using terminal thiols and maleimide handles.

  • Useful for feasibility builds and research constructs
  • Handle planning reduces multi-site mixtures
  • Stabilized designs can be considered
Amide coupling

Activated ester routes when suitable handles are available.

  • Useful when click handles are constrained
  • Requires strict control to limit heterogeneity
  • Often paired with protected handles
Cleavable linkers

Selected when intracellular release is 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

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

Design inputs & coupling routes (solid-phase vs solution-phase)

Design inputs we review

Practical peptide–DNA design starts with constraints. We review DNA format, length, modification map, and attachment site options to propose a handle + linker plan that preserves DNA integrity and limits conjugate heterogeneity.

  • DNA format: ssDNA vs dsDNA; strand/terminus selection
  • Attachment location: 5′ / 3′ or internal handle placement (program-dependent)
  • Peptide selection: targeting ligands vs CPP concepts; charge/hydrophobicity constraints; optional branching
  • Linker choice: stable vs cleavable; spacer length (PEG/alkyl) to manage sterics and solubility
  • Purification strategy: RP-HPLC / IEX / SEC selection based on construct polarity and size
Two common coupling routes

Peptide–DNA conjugates can be assembled by solid-phase or solution-phase coupling. Route selection depends on DNA chemistry, handle availability, and purification strategy.

  • Solid-phase: coupling while the oligonucleotide is on-support; useful when the handle is introduced during DNA synthesis
  • Solution-phase: coupling purified components via click, maleimide, or amide chemistries
  • Monitoring: in-process checks can be applied to track conversion and byproduct formation
  • Workup: conditions selected to preserve DNA integrity and conjugate homogeneity
Mechanism note (CPPs and targeting peptides)

Peptides used in DNA 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.

Note: uptake and activity are sequence- and context-dependent; we focus on providing well-defined materials and documentation suitable for your program stage.

Workflow / procedure

Typical workflow for peptide–DNA conjugate synthesis, purification, and analytical control
Typical workflow for peptide–DNA conjugate synthesis, purification, and analytical control.
  • DNA design & modification map – Confirm DNA format (ssDNA/dsDNA), length, and desired modification/handle placement.
  • Handle installation – Introduce compatible functional handles (thiol, amine, azide/alkyne, DBCO/BCN) at the chosen position.
  • Peptide–DNA conjugation – Perform chemoselective coupling with controlled conditions and conversion monitoring.
  • Purification – Isolate the desired conjugate and remove unreacted components (e.g., HPLC/IEX/SEC as appropriate).
  • Analytical QC + release – Confirm identity/conjugation and provide 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.

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
  • DNA-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.

Our Quality Commitment

Bio-Synthesis is committed to Total Quality Management (TQM) to ensure consistent quality, traceability, and customer satisfaction across DNA synthesis, peptide synthesis, and peptide–DNA conjugation services.

Each DNA–peptide conjugate is produced under controlled procedures with in-process monitoring and final analytical verification. Identity confirmation is performed by mass spectrometry, and purity is assessed using HPLC and/or capillary gel electrophoresis, as appropriate for the construct.

Purification and quality assurance (QA) procedures are applied to deliver high-quality oligo–peptide conjugates suitable for reproducible research and development workflows. Our quality system follows ISO 9001–aligned practices, with documentation and release criteria scaled to the intended use and program stage.

FAQ

What DNA formats do you support for peptide conjugation?

We support peptide conjugation to ssDNA, dsDNA (typically annealed constructs), and selected modified DNA designs when compatible handles and linkers are defined.

Which conjugation chemistry should I choose?

Copper-free click is a common default for site specificity and oligonucleotide compatibility. 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.

Can you attach peptides to the 5′ or 3′ end of DNA?

Yes. Site-defined attachment is commonly implemented at the 5′ or 3′ terminus using functional handles (amine, thiol, azide/alkyne). Internal handle placement can be evaluated on a project basis.

What do you need for a quote?

Send DNA format, sequence length, modification pattern, peptide sequence/handle, preferred attachment site (or constraints), linker preference (or “recommend”), and quantity/purity targets.

Contact & quote request

For the fastest quote, send DNA format (ssDNA/dsDNA), sequence length, modification/handle details, peptide sequence/handle, preferred attachment site (or constraints), linker preference (or “recommend”), and quantity/purity targets.

Fastest path
Fast quote checklist
  • DNA format (ssDNA/dsDNA) + sequence length
  • Modification pattern + handle placement (5′/3′/internal)
  • Peptide sequence + desired attachment preference
  • Linker preference (or “recommend”) + cleavable vs stable
  • Quantity (mg) + purity target + intended use

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

Recommended reading

Journal-style references that cover oligonucleotide chemistry, delivery, and peptide/ligand conjugation strategies relevant to peptide–DNA constructs.

  • Crooke ST, Baker BF, Crooke RM, Liang XH. Antisense technology: an overview and prospectus. Nat Rev Drug Discov. 2021. Article
  • Shen X, Corey DR. Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs. Nucleic Acids Res. 2018;46(4):1584–1600. DOI
  • Juliano RL. The delivery of therapeutic oligonucleotides. Nucleic Acids Res. 2016;44(14):6518–6548. DOI
  • Winkler J. Oligonucleotide conjugates for therapeutic applications. Ther Deliv. 2013;4(7):791–809. DOI
  • Malinowska AL, Huynh HL, Bose S. Peptide–Oligonucleotide Conjugation: Chemistry and Therapeutic Applications. Curr Issues Mol Biol. 2024;46(10):11031–11047. DOI
  • Klabenkova K, Fokina A, Stetsenko D. Chemistry of Peptide-Oligonucleotide Conjugates: A Review. Molecules. 2021;26(17):5420. DOI
  • Fàbrega C, Aviñó A, Navarro N, Jorge AF, Grijalvo S, Eritja R. Lipid and Peptide-Oligonucleotide Conjugates for Therapeutic Purposes: From Simple Hybrids to Complex Multifunctional Assemblies. Pharmaceutics. 2023;15(2):320. DOI

If you want, we can also provide a concise, PDF-friendly “IND appendix” version of key definitions and analytical deliverables tailored to your program stage.

Why Choose Bio-Synthesis

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