Use of homoarginine to obtain attenuated cationic membrane lytic peptides

Kentarou Sakamoto, Misao Akishiba, Takahiro Iwata, Jan Vincent V. Arafiles, Miki Imanishi, Shiroh Futaki

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Our research group has been studying the design of intracellular delivery peptides based on cationic lytic peptides. By placing negatively charged amino acids on potentially hydrophobic faces of the peptides, membrane lytic activity is attenuated on the cell surface, whereas it recovers in endosomes, enabling cytosolic delivery of proteins including antibodies. These lytic peptides generally contain multiple lysines, facilitating cell surface interaction and membrane perturbation. This study evaluated the effect of lysine-to-homoarginine substitution using HAad as a model delivery peptide. The resulting peptide had a comparable or better delivery efficacy for Cre recombinase, antibodies, and the Cas9/sgRNA complex with one-quarter of the concentration of HAad, implying that a subtle structural difference can affect delivery activity.

Original languageEnglish
Pages (from-to)127925
Number of pages1
JournalBioorganic and Medicinal Chemistry Letters
Publication statusPublished - May 15 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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