Use of homoarginine to obtain attenuated cationic membrane lytic peptides

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