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DNA – peptide conjugates

DNA-peptide conjugates or oligo-peptide conjugates are composed of single stranded DNA linked to a synthetic peptide. Also known as peptide-oligonucleotide conjugates (POCs), they are primarily intended for cellular delivery, that is, pulling DNA oligos into cells by means of a transporter peptide.

At AltaBioscience, we offer different options for conjugation either at the 3’ end of the oligo or at the 5’ prime end depending on your requirements. In addition, the linkage between the DNA-peptide can be either a stable covalent bond or a reducible disulphide bridge as needed for your application.

We offer a range of dyes and labels that can also be added on either or both DNA and peptide elements. Please contact us to check options for labelling to ensure method compatibility.

Whilst not essential, we recommend a phosphorothioate backbone for DNA conjugates to reduce the chance of enzymatic cleavage.

AltaBioscience can provide custom synthesis of both the required peptide and oligonucleotide but we are happy to discuss conjugation projects using your own DNA or peptide.

Conjugation methods

We offer several conjugation options using post-synthesis techniques to conjugate the peptide and oligonucleotide.

Both the peptide and DNA are synthesised independently using solid phase techniques then keeping either the peptide or oligo immobilised on a solid support, conjugation is performed post-synthesis. Both the peptide and oligo undergo HPLC purification prior to conjugation with the final conjugate being purified by desalting methods.

The N or C terminus of the peptide is often used as a conjugation site with either the 3’ or 5’ ends of the DNA. The most common linkage options are:

  • Disulfide linkage using thiol groups on both the peptide and DNA molecules (non-stable, suitable for reduction to separate DNA and peptide)
  • Amide bond linkage via a thiol and amino group on the DNA and peptide (stable bond)

Modifications can be incorporated on either the DNA or peptide molecule or where suitable on both molecules. Modifications include:

  • Dye labelling including but not limited to
    • FAM
    • TAMRA
    • BHQ1
    • BHQ2
  • Biotinylation
  • Spacers
  • Modified amino acids incorporated in peptide sequence
  • Modified bases on the oligonucleotide
  • Phosphorothioate linkage on the backbone of the oligonucleotide molecule

DNA Peptide applications

DNA-peptide applications are varied and we are able to work with customers to provide conjugates which are tailored to their requirements.

A common strategy is to combine a cell penetrating carrier peptide with a strand of phosphorothioate DNA reinforced against nuclease attack. Conjugates like this can be used in ‘knock-out’ studies to investigate the effects of gene expression and how multiple genes interact.

DNA Peptide conjugation services

As well as peptide conjugation services, AltaBioscience provides custom dna oligo synthesis, custom peptide synthesis and conjugation of peptides to DNA oligo. We also have a range of stock cell penetrating peptides ready for conjugating to your modified DNA or DNA synthesised by AltaBioscience.

For more information, please email us at info@altabioscience.com or call us on +44(0)1527 584495 to speak to one of our experts.