Peptide–oligo conjugates are innovative hybrid molecules uniting the targeting precision of peptides with the gene-modulating power of oligos. However, harnessing their potential requires overcoming significant technical barriers...
Liu, J., Heddleston, J., Perkins, D.R., Chen, J.J.H., Ghanbarpour, A., Smith, B.W., Miles, R., Aihara, E. and Afshar, S. Scientific Reports 14, no. 1 (2024): 13437.
- Protein Engineering, Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, 92121, USA
- Biotechnology Research, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, 46221, USA
- Genetic Medicine, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, 46221, USA
Synthetic peptides were ordered from CPC scientific with > 95% purity. NNJA peptides in the formats of monomer or dendrimer were conjugated by click chemistry to siRNA targeting hypoxanthine–guanine phosphoribosyltransferase (HPRT) gene [..]
Hao, Liangliang, Renee T. Zhao, Nicole L. Welch, Edward Kah Wei Tan, Qian Zhong, Nour Saida Harzallah, Chayanon Ngambenjawong et al. Nature Nanotechnology (2023): 1-10.
All peptides and oligonucleotides were synthesized and HPLC purified by CPC Scientific and Integrated DNA Technologies (IDT), respectively. Peptide–oligonucleotide conjugates were generated by copper-free click chemistry.
Synthetic oligonucleotides constitute an important class of therapeutics developed to treat a variety of indications. Two main synthetic approaches exist for the conjugation of a peptide to an oligonucleotide: parallel and linear. The primary benefit of the linear approach is the one-pot solid-phase assembly and compatibility with machine automation. However, in cases where poor compatibility of peptide and oligo chemistries exist or long peptide and oligo fragments are required, preparing both components separately and linking both compounds together may offer the simplest solution.
