Custom DNA-Peptide Conjugates

Bio-Synthesis offers high quality DNA-Peptide Conjugates by employing selective cross-linking chemistries. We provide a wide variety of synthesis scales, modifications, treatments and purifications to customize your conjugates to exacting requirements. These oligonucleotide-peptide conjugates (OPCs) are used in a variety of biological applications. One of the most common and increasingly important properties of such hybrids is a significant improvement in cellular uptake, where the peptide acts as an exceptionally versatile carrier.

As specialists in bioconjugation, we employ a variety of cross-linking chemistries including (but not limited to) native ligation chemistry and click chemistry. Each oligo-peptide hybrid is meticulously monitored during the production cycle, ensuring adherence to our stringent quality control standards. The final product is characterized by mass spectrometry, and its purity is analyzed using high throughput capillary gel electrophoresis.

Bio-Synthesis DNA-Peptide Conjugate Services

  • Wide variety of synthesis scales, modifications, treatments and purifications.
  • Oligo peptide conjugates such as: DNA conjugates, RNA conjugates, siRNA conjugates and BNA conjugates.
  • Fully traceable documentation system.

High Quality DNA-Peptide Conjugates

Bio-Synthesis is committed to Total Quality Management (TQM) to assure customer satisfaction. MS and HPLC analyses are performed following the completion of DNA, peptide syntheses and DNA-peptide conjugates. Purification and QA (quality assurance) procedures guarantee high quality oligo-peptide conjugates. We employ Total Quality Management (TQM) complying with ISO 9001:2008 regulations.

Specification of DNA-Peptide Conjugates

Requirements Peptide Oligonucleotide
Length* 2 - 30 amino acids 8-40 DNA bases, 2'OMe, 2'F-RNA, 5'-methyl dC, 2-amino-dA
Purity >85-95% C-5 propynyl-C and C-5 propynyl-U
Modification None HPLC purified
Chimeric oligo: PS/PO mixture
Additional dye modification (such as Fluorescein or CY3)
*Longer peptide oligonucleotide sequences are available upon request.
Conjugate yield in OD 1-2 ODs 5 ODs 10 ODs > 10 ODs
Optical density at λ= 260 nm

Peptide-DNA Conjugate Services:

  • BNA/DNA-peptide synthesis and conjugation
  • Peptide nucleic acid conjugates
  • DNA-peptide-DNA conjugation
  • DNA-peptide-BNA hybrids
  • DNA-Peptide-BNA*
  • Double strand DNA-peptide conjugation
  • Peptide-DNA-peptide conjugates
  • Coupling of a single amino acid to DNA
  • Coupling peptides with BNA, LNA, BNA, ZNA, morpholino or other nucleic acid analogues
  • Labeling of peptide-DNA conjugates with fluorescent dye or other modifications

* We offer custom BNA oligonucleotide synthesis as an alternative to LNA


Prices vary depending on the method used in obtaining peptide-oligo conjugates. Please contact us for a quotation.

Oligo-Peptide Conjugation Chemistry

Oligonucleotide-Peptide conjugates (OPCs) are chimeric molecules composed of a nucleic acid portion covalently linked to a peptide. Potential applications for oligo-peptide constructs are in fields ranging from therapeutics to nanotechnology. Oligonucleotides have been attached to a number of peptides to enhance the cellular membrane permeability1,2 and study the molecular requirements for enzyme activity3. In addition, oligonucleotide-peptide conjugates have been used in several sensing systems4 . When conjugated to peptides, oligonucleotides are more resistant to nculeases5 and enhance duplex formation when linked to cationic peptide6.

Conjugation of these large and functionalized molecules is often hindered by side-reactions. To overcome such difficulty, we apply different synthetic approaches for the chemical synthesis of oligonucleotide peptide conjugates. The two most common approaches are:

  • Total stepwise synthesis (or in-line solid phase synthesis)
  • Post-synthetic conjugation (or post-assembly conjugation, fragment coupling strategy)

Stepwise synthesis is an in-line solid phase synthesis protocol where the peptides and oligonucleotides are usually synthesized sequentially on the same solid support. Post-synthetic conjugation is a chemoselective ligation reaction of reactive groups that are introduced into oligonucleotides and peptides. This strategy includes the formation of several linkages such as amide, disulfide, oxime, carbonyl linkages or cycloaddition click reactions.

Although, the price for using other strategies for making peptide-oligo conjugate is the same, the price for obtaining other modified peptides, DNA oligo or different conjugation chemistries that include either stable or cleavable linkages may be higher.


Product is HPLC purified and usually over 85-95% pure


All our processes are subject to strict quality control procedures. Analytical HPLC and MS analyses are performed in every development cycle. Final target conjugates must first be isolated from excess or unreacted reagents by gel filtration. Size-exclusion chromatography (SEC) or reverse phase HPLC may be used to either remove excess reagent or isolate and characterize the cross-linked product. Once the product has been purified,it may be subject to many different types of studies including spectroscopy (MALDI-TOF,ESI, LC-MS Fluorescence) and electrophoresis.

QC (quality control) and QA (quality assurance) procedures are performed independently to insure the highest quality conjugates. The final quantity is validated by UV absorbance at 260 nm.Moreover, we will monitor your project through every step and keep you informed of the latest progress.

Delivery Specifications

A typical delivery consists of alyophilized sample in individually labeled vials.The shipment also contains COA, MS, HPLC and/or other analytical data. Additional analytical data is also available upon request.

Contact our Technical Service Center at 800.227.0627 or contact us online with detailed oligo-peptide project specifications. A project manager will be assigned to help you to design an appropriate synthetic method for your specific needs.


1. Gait, M.J. Peptide-mediated cellular delivery of antisense oligonucleotides and their analogues. Cell. Mol. Life Sci. 2003, 60, 844–853.

2. Said, H.F.; Saleh, A.F.; Abes, R.; Gait, M.J.; Lebleu, B. Cell penetrating peptides: Overview and applications to the delivery of oligonucleotides. Cell. Mol. Life Sci. 2010, 67, 715–726.

3. Mazzini, S.; García-Martin, F.; Alvira, M.; Aviñó, A.; Manning, B.; Albericio, F.; Eritja, R.Synthesis of oligonucleotide derivatives using ChemMatrix supports. Chem. Biodivers. 2008, 5, 209–218.

4. Merkoçi, A.; Aldavert, M.; Tarrasón, G.; Eritja, R.; Alegret, S. Toward an ICPMS-Linked DNA assay based on gold nanoparticles immunoconnected through peptide sequences. Anal. Chem. 2005, 77, 6500–6503.

5. Robles, J.; Maseda, M.; Beltrán, C.M.; Pedroso, E.; Grandas, A. Synthesis and enzymatic stability of phosphodiester-linked peptide-oligonucleotide hybrids. Bioconjug. Chem. 1997, 8, 785–788.

6. Corey, D.R. 48000-Fold acceleration of hybridization by chemically-modified oligonucleotides. J. Am. Chem. Soc. 1995, 117, 9373–9374.

Oligo conjugation related services

Ordering and Submitting Requests for Bioconjugation Services

For us to better understand your customized project, please complete our Bioconjugation Service Questionnaire. The more our chemists understand your project needs, the more accurate feedback we will be able to provide you.  Provide us with your project details will enable to us to recommend the best reagents to use for your project.  The most useful and readily available tools for bioconjugation projects are cross-linking reagents. A large number of cross-linkers, also known as bifunctional reagents, have been developed.  There are several ways to classify the cross-linkers, such as the type of reactive group, hydrophobicity or hydrophilicity, and the length of the spacer between reactive groups.  Other factors to consider are whether the two reactive groups are the same or different (for example, heterobifunctional or homobifunctional reagents), whether the spacer is cleavable, and whether the reagents are membrane permeable or impermeable.  The most accessible and abundant reactive groups in proteins are the ϵ-amino groups of lysine.  Therefore, a large number of the most common cross-linkers are amino selective reagents, such as imidoesters, , sulfo-N-hydroxysuccinimide esters, and N-hydroxysuccinimide esters.  Due to the high reactivity of the thiol group with N-ethylmaleimide, iodoacetate and a-halocarbonyl compounds, new cross-linkers have been developed that contain maleimide and a-carbonyl moieties.  Usually, N-alkylmaleimides aremore stable than their N-aryl counterparts.

In addition to the reactive groups on the cross-linkers, a wide variety of connectors and spacer arms have also been developed.  The nature and length of the spacer arm play an important role in the functionality.  Longer spacer arms are generally more effective when coupling large proteins or those with sterically protected reactive side-chains.  Other important considerations are the hydrophobicity, hydrophilicity, and the conformational flexibility.  Long aliphatic chains generally fold on themselves when in an aqueous environment, which makes the actual distance spanned by such linker arms less than expected.  Instead, spacers that contain more rigid structures (for example, aromatic groups or cycloalkanes) should be used.  These structures, however, tend to be very hydrophobic which could significantly decrease the solubility of the modified molecules or even modify some of their properties.  In such cases, it is recommended to choose a spacer that contains an alkylether (PEO) chain.  Bio-Synthesis offers several cross-linkers with PEO chains, such as thiol-binding homobifunctional reagents, heterobifunctional based, and their derivatives.

Within 3-5 days upon receiving your project scope, we will provide you an appropriate quotation. An order can be placed with PO (Purchase Order) or major credit cards ( ). Your credit card will be billed under Bio-Synthesis, Inc.