1. Use of homoarginine to obtain attenuated cationic membrane lytic peptides.
- Author
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Sakamoto K, Akishiba M, Iwata T, Arafiles JVV, Imanishi M, and Futaki S
- Subjects
- Amino Acid Sequence, CRISPR-Associated Protein 9 pharmacology, Dextrans chemistry, Drug Carriers toxicity, Drug Liberation, Fluoresceins chemistry, Fluorescent Dyes chemistry, HeLa Cells, Humans, Immunoglobulin G pharmacology, Integrases pharmacology, Liposomes chemistry, Peptides toxicity, Sulfonic Acids chemistry, RNA, Guide, CRISPR-Cas Systems, Drug Carriers chemistry, Endosomes metabolism, Homoarginine chemistry, Intracellular Membranes metabolism, Peptides chemistry
- Abstract
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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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