Peptide-oligonucleotide Conjugation

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Oligonucleotides and their analogs can be used as inhibitors of gene expression for antisense mechanism research of target RNAi. They can form triple-stranded structure with double-stranded DNA and can also act as aptamers of proteins. Thus oligonucleotides and its analogues are important drug molecules.
Protein is a biologically functional substance, but its molecular structure is complex, and many uncertain factors are set for its application. The peptide structure is simple, natural extraction or artificial synthesis is relatively easy, and the peptide has better membrane permeability than oligonucleotide. Conjugated oligonucleotides and peptides by covalent attachment can enhance the function of the oligonucleotide. Studies have shown that peptide and oligonucleotide conjugates have stronger target cell penetration and higher cell absorption efficiency than unmodified oligonucleotides.

Preparation of peptide and oligonucleotide conjugates

There are several different strategies for synthesizing peptide and oligonucleotide conjugates, including solid phase synthesis, liquid phase synthesis, and biosynthesis. When the peptide is conjugated to the oligonucleotide, the peptide is capable of binding to the base of the oligonucleotide, the 3 or 5 end of the ribose or the phosphate backbone. Likewise, the point of attachment of the oligonucleotide and peptide can be the C-terminus, N-terminus or amino acid side chain of the peptide.

Peptide-oligonucleotide Conjugation Fig.1 Total stepwise synthesis of oligonucleotide-(3-N)-peptide conjugates on a homoserine functionalized support (Stetsenko et al. 2005)

Our Services

As the world's leading peptide synthesizer and supplier, Creative Peptides has experienced experts and leading-edge technology to provide high quality peptide-oligonucleotide conjugates. We offer different synthesis ratios, which can be modified, processed and purified according to customers’ requirements to achieve the most precise requirements.

The peptide-oligonucleotide conjugates we provide can be used:

We have strict control over the products in the production process to ensure strict quality control standards. The final product is analyzed by different methods and finally delivered to customers with high quality products.


  1. Singh, Y., Murat, P., & Defrancq, E. (2010). Recent developments in oligonucleotide conjugation. Chemical Society Reviews, 39(6), 2054-2070.
  2. Graham, D., & Enright, A. (2006). Cycloadditions as a method for oligonucleotide conjugation. Current Organic Synthesis, 3(1), 9-17.
  3. Tung, C. H., Rudolph, M. J., & Stein, S. (1991). Preparation of oligonucleotide-peptide conjugates. Bioconjugate chemistry, 2(6), 464-465.
  4. Stetsenko, D. A., & Gait, M. J. (2005). Chemical methods for peptide-oligonucleotide conjugate synthesis. In Oligonucleotide Synthesis (pp. 205-224). Humana Press.
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