Peptide-oligonucleotide Conjugation

Peptide-oligonucleotide Conjugation

At Creative Peptides, we specialize in custom peptide-oligonucleotide conjugation (POC) — a cutting-edge technique that integrates peptide synthesis and oligonucleotide modification to create multifunctional molecules with enhanced stability, delivery, and biological performance. Our expert chemists combine advanced solid-phase synthesis, precise linker design, and analytical validation to deliver high-quality conjugates tailored to your research or therapeutic needs. Whether you are developing antisense oligonucleotides, siRNA therapeutics, or peptide-based delivery systems, we provide reliable, scalable, and cost-effective POC solutions from design to production.

What Problems Does This Technology Solve?

Traditional nucleic acid drugs often face challenges such as poor cellular uptake, limited tissue targeting, rapid degradation, and inefficient endosomal escape.

Peptide-oligonucleotide conjugation directly addresses these bottlenecks by:

Improving delivery efficiency: Cell-penetrating and targeting peptides enable precise delivery of nucleic acids into desired cells or tissues.

Enhancing molecular stability: Peptide conjugation protects oligonucleotides from enzymatic degradation in biological environments.

Boosting therapeutic potency: Optimized linkers and cleavable bonds ensure controlled release and high bioavailability.

Enabling multifunctionality: Combines the biological specificity of oligonucleotides with the structural and targeting diversity of peptides for next-generation therapeutics and diagnostics.

Our Peptide-Oligonucleotide Conjugation (POC) Service Offerings

We provide comprehensive, end-to-end peptide-oligonucleotide conjugation services designed to meet the stringent requirements of research, preclinical, and GMP manufacturing stages. Each service module is fully customizable and supported by expert chemists with extensive experience in peptide synthesis, oligonucleotide chemistry, and advanced bioconjugation techniques.

Custom Design & Strategy Consultation

Every successful conjugation begins with thoughtful molecular design. Our scientists collaborate closely with you to define:

The molecule type (ASO, siRNA, PNA, aptamer, mRNA, etc.) and its desired function.

The peptide role—cell-penetrating, targeting, or responsive.

The linker system (cleavable, non-cleavable, PEGylated, or stimuli-responsive).

The optimal conjugation chemistry (thiol–maleimide, click, disulfide, EDC/NHS).

We then propose a complete technical roadmap, estimated yield, project timeline, and analytical plan — ensuring transparency from concept to delivery.

High-Quality Peptide Synthesis

Our peptide synthesis platform utilizes solid-phase peptide synthesis (SPPS) with state-of-the-art automated synthesizers and controlled reaction monitoring.

Linear, cyclic, stapled, and D-/L-amino acid peptides.

Peptides bearing functional handles (–SH, –NH2, azide, alkyne, maleimide).

Custom modifications such as acetylation, amidation, PEGylation, lipidation, fluorophore labeling, and isotope tagging.

Analytical validation by HPLC, LC-MS, MALDI-TOF, and amino acid analysis.

Our peptide team ensures every batch meets high purity and identity standards, suitable for both research-grade and GMP manufacturing.

High-Quality Oligonucleotide Synthesis

We synthesize DNA, RNA, ASO, siRNA, PNA, and aptamers with precise control over sequence fidelity, modification pattern, and scale.

Automated solid-phase oligonucleotide synthesis (up to 120 bases).

Backbone and sugar modifications: phosphorothioate (PS), 2'-O-methyl, 2'-fluoro, LNA, MOE, and others.

Incorporation of reactive groups (thiol, amine, azide, alkyne, biotin, fluorescent dyes).

Rigorous purification (HPLC/UPLC) and characterization by LC-MS and UV spectroscopy.

Our oligo chemistry team ensures precise coupling efficiency and minimal depurination for highly stable conjugation substrates.

Precision Conjugation & Reaction Optimization

Using validated, site-specific chemistries, we perform controlled peptide–oligonucleotide conjugation under optimized conditions to maximize yield and maintain structural integrity.

5′-, 3′-, or internal position conjugation with linker length optimization.

Multiple conjugation strategies (click, thiol–maleimide, disulfide, oxime, amidation).

Evaluation of reaction stoichiometry, linker flexibility, and conjugate stability.

Parallel screening to identify the most effective conjugation route for your molecule.

All reactions are monitored in real time using analytical LC and UV profiles to ensure reproducibility.

Purification, Analytical Characterization & Quality Control

Each conjugate undergoes comprehensive purification and analytical verification to ensure chemical purity, sequence accuracy, and biophysical stability.

RP-HPLC / UPLC purification.

LC-MS and MALDI-TOF mass confirmation.

UV/Vis quantification and oligonucleotide–peptide ratio determination.

Stability testing under variable pH and temperature conditions.

CoA (Certificate of Analysis) and complete QC report with raw data traceability.

Scale-Up, GMP Manufacturing & Documentation

We provide scalable synthesis solutions — from milligram-scale research batches to gram-scale GMP manufacturing suitable for IND-enabling studies.

Our manufacturing features:

GMP-compliant environment for oligonucleotide and peptide production.

Controlled documentation and batch record management for regulatory submission.

Optional technology transfer support for partners seeking in-house scale-up.

Seamless transition from discovery to clinical-grade supply.

Delivery & Functional Validation Support(Optional)

To complement chemical conjugation, we offer biological evaluation and functional testing support through partner laboratories.

Available assays:

Cellular uptake and localization studies (fluorescence imaging, flow cytometry).

In-vitro gene silencing efficiency (RT-qPCR, Western blot).

Nuclease resistance and serum stability assays.

In-vivo biodistribution and PK/PD support upon request.

Choice of Peptide for Conjugation

Selecting the right peptide is critical to achieving optimal delivery efficiency and biological performance. We offer a wide portfolio of custom and catalog peptides designed for different therapeutic and diagnostic goals.

Cell-Penetrating Peptides (CPPs)

Facilitate membrane translocation of oligonucleotides

TAT, Penetratin, R8, Transportan, Pep-1

siRNA / ASO delivery, intracellular imaging

Enhance cellular uptake and endosomal escape

Targeting Peptides

Direct conjugates to specific cells or tissues

RGD, NGR, cRGDfK, Angiopep-2, MSH analogs

Tumor targeting, brain delivery, receptor-mediated uptake

Improve selectivity and tissue specificity

Endosomal Escape Peptides

Promote release of nucleic acids from endosomes

INF7, GALA, HA2, KALA

siRNA / mRNA delivery, endosome-sensitive systems

Increase cytosolic delivery efficiency

Nuclear Localization Peptides (NLS)

Transport conjugates into the nucleus

PKKKRKV, SV40 NLS, M9

Gene regulation, antisense therapy

Enhance nuclear access and transcriptional control

Mitochondrial Targeting Peptides

Direct oligonucleotides to mitochondria

MTS (COX8a)

Mitochondrial disease research, RNA therapeutics

Enable organelle-specific targeting

Cleavable / Responsive Peptides

Release oligonucleotide under specific conditions

Enzyme-cleavable linkers, acid-labile motifs

Controlled release in tumor microenvironment

Tunable release and improved safety

Custom Peptides

Tailor-made sequences for novel delivery systems

Designed per project need

Any nucleic acid platform (ASO, siRNA, PNA, Aptamer)

Fully customizable to meet project objectives

Oligonucleotide Molecule Types We Support

Our peptide–oligonucleotide conjugation platform supports a wide range of nucleic acid molecules used across drug discovery, diagnostics, and therapeutic delivery. Each molecule type has unique structural and functional features that influence conjugation chemistry, linker design, and peptide selection.

ASO

Antisense Oligonucleotide – short single-stranded DNA or RNA designed to modulate gene expression

Phosphorothioate (PS) backbone, 2'-O-methyl, 2'-MOE, LNAs

Gene silencing, splice modulation, RNA knockdown

Improves stability and tissue uptake via peptide conjugation

siRNA

Small Interfering RNA – double-stranded RNA molecules (typically 21–23 nt) that trigger RNA interference

2'-O-methyl, 2'-F, phosphorothioate ends, blunt or overhang design

Gene knockdown, therapeutic RNAi

Enhances cell penetration, endosomal escape, and in vivo delivery

PNA

Peptide Nucleic Acid – synthetic analog with peptide-like backbone

N-terminal labeling, lysine or cysteine handles, fluorescent tags

Antisense inhibition, molecular probes, diagnostics

High binding affinity and chemical stability; easy conjugation with peptides

Aptamer

Single-stranded DNA/RNA that folds into 3D structure for target binding

Biotin, amine, thiol, azide handles, PEGylation

Targeted delivery, biomarker detection, therapeutic blocking

Peptide conjugation adds targeting or extended circulation

mRNA / saRNA

Messenger or self-amplifying RNA for protein expression

Cap analogs, modified nucleotides (Ψ, m5C), 5'/3' UTR engineering

Vaccines, protein replacement therapies

Peptide fusion or conjugation improves translation and cellular entry

DNA Probes / Oligos

Custom DNA sequences for hybridization, labeling, or detection

Fluorescent tags, spacers, linkers, biotin

Molecular diagnostics, imaging, biosensing

Enables controlled immobilization and multiplex detection

Why Our POC Development Platform Stands Out

Precision Chemistry

Site-specific conjugation ensures consistent molecular orientation and reproducible bioactivity.

Broad Molecule Compatibilit

Fully compatible with ASO, siRNA, PNA, aptamer, and mRNA platforms.

Diverse Peptide Options

Access to a wide catalog of cell-penetrating, targeting, and endosomal escape peptides for customizable delivery.

Enhanced Delivery Efficiency

Peptide conjugation significantly improves cell uptake, tissue targeting, and endosomal release of oligonucleotides.

Improved Stability

Chemical conjugation protects nucleic acids from enzymatic degradation and extends in-vivo half-life.

Flexible Scale & GMP Support

From discovery to clinical manufacturing, scalable production with full documentation and regulatory compliance.

Comprehensive Analytical Support

Every batch is verified by LC-MS, HPLC, and functional testing to meet stringent purity and identity standards.

Fast Turnaround & Technical Expertise

Expert chemists with extensive peptide and oligonucleotide synthesis experience deliver reliable results on schedule.

One-Stop Solution

Integrated design, synthesis, conjugation, and characterization services eliminate multi-vendor coordination.

Peptide-Oligonucleotide Conjugation Service Workflow

Our streamlined workflow ensures precision, traceability, and reproducibility at every stage of your project — from concept to final conjugate delivery.

1

Project Consultation & Design Planning

Define molecular type (ASO, siRNA, PNA, aptamer), peptide selection, conjugation chemistry, linker type, and scale.

We provide a detailed technical proposal, estimated yield, lead time, and quotation.

2

Peptide & Oligonucleotide Synthesis

Solid-phase synthesis (SPPS and automated DNA/RNA synthesis) with functional handles (–SH, –NH₂, azide, alkyne, biotin, etc.).

All intermediates are verified by LC-MS and analytical HPLC.

3

Conjugation & Optimization

Site-specific peptide–oligonucleotide coupling using validated chemistries (thiol–maleimide, click, EDC/NHS, disulfide, etc.).

Optimization of linker length, spacer type, and reaction efficiency for high yield and purity.

4

Purification & Analytical Characterization

Purification by RP-HPLC or UPLC, followed by LC-MS, UV/Vis, and stability testing.

Full analytical report including purity, sequence confirmation, and storage recommendations.

5

Scale-Up, Documentation & Delivery

Scalable production from milligram R&D batches to gram-level GMP materials.

Delivery includes batch records, certificates of analysis (CoA), and QC data package.

Application Fields of Peptide-Oligonucleotide Conjugation

Peptide-oligonucleotide conjugation (POC) technology has broad utility across therapeutics, diagnostics, and biotechnology research. Below are the major application areas and how this technology is applied in each:

Antisense and siRNA Therapeutics

Enhance Cellular Uptake: CPP-ASO or CPP-siRNA conjugates cross cell membranes efficiently.

Improve Tissue Targeting: Targeting peptides (e.g., RGD, Angiopep-2) guide oligonucleotides to tumor or CNS tissues.

Increase Bioavailability: Conjugation protects ASOs/siRNAs from nuclease degradation and boosts in-vivo stability.

Facilitate Endosomal Escape: Specialized peptides (INF7, GALA) promote cytoplasmic release for improved gene silencing efficacy.

mRNA and Gene-Editing Delivery

mRNA Delivery Enhancement: Peptide conjugation improves intracellular delivery and translation efficiency of mRNA vaccines or therapeutics.

CRISPR System Delivery: POC supports delivery of sgRNA/Cas components using targeting or nuclear localization peptides.

Self-amplifying RNA (saRNA) Systems: Boosts endosomal release and protein expression levels in saRNA platforms.

Aptamer-Based Targeting & Diagnostics

Targeted Drug Delivery: Peptide-aptamer conjugates combine high specificity of aptamers with tissue-directing peptides.

Molecular Recognition & Imaging: Fluorescent or biotin-tagged POC constructs are used for biomarker detection.

Enhanced Binding Affinity: Peptide modification stabilizes aptamer folding and improves binding under physiological conditions.

Peptide Nucleic Acid (PNA) and Probe Design

Hybridization-Based Detection: PNA-peptide conjugates serve as high-specificity probes for in-situ hybridization or biosensors.

Antisense Research: Increase cellular delivery of PNAs for gene regulation studies.

Labeling & Tracking: Peptide tags allow controlled immobilization or tissue localization of probes.

Biomaterials and Nanomedicine

Surface Functionalization: Peptide-oligonucleotide hybrids decorate nanoparticles, liposomes, or hydrogels for smart drug release.

Stimuli-Responsive Systems: Incorporation of cleavable or pH-sensitive linkers enables controlled release in microenvironments.

Theranostics: Dual-function conjugates for simultaneous diagnosis and therapy (imaging + RNA interference).

Start Your Peptide-Oligonucleotide Conjugation Project Today

Ready to take your nucleic acid research to the next level? Partner with Creative Peptides, a global provider of custom peptide-oligonucleotide conjugation, bioconjugation chemistry, and delivery optimization solutions. From design to GMP manufacturing, our experts deliver precision-engineered conjugates tailored to your therapeutic or diagnostic goals. Contact us today to discuss your project or request a free consultation and quotation.

FAQs

We support DNA, RNA, ASO, siRNA, PNA, aptamers, and mRNA with multiple chemical backbones (PS, 2'-O-Me, 2'-F, LNA, etc.).

We use click chemistry (CuAAC/SPAAC), thiol-maleimide, disulfide exchange, EDC/NHS amidation, and other site-specific linkers depending on the molecular handles.

Yes. Our platform supports research-scale and GMP-compliant manufacturing with full documentation, traceability, and CoA.

Each conjugate is analyzed by LC-MS, HPLC/UPLC, UV-Vis spectroscopy, and stability testing to confirm purity, identity, and integrity.

Absolutely. Our scientists can assist in sequence design, selection of conjugation sites, and optimization of physicochemical properties to meet your biological objectives.