Modular Redesign of a Cationic Lytic Peptide To Promote the Endosomal Escape of Biomacromolecules
Dr. Yusuke Azuma
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorHaruka Imai
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorDr. Yoshimasa Kawaguchi
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorProf. Dr. Ikuhiko Nakase
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorProf. Dr. Hiroshi Kimura
Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503 Japan
Search for more papers by this authorCorresponding Author
Prof. Dr. Shiroh Futaki
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorDr. Yusuke Azuma
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorHaruka Imai
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorDr. Yoshimasa Kawaguchi
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorProf. Dr. Ikuhiko Nakase
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorProf. Dr. Hiroshi Kimura
Institute of Innovative Research, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503 Japan
Search for more papers by this authorCorresponding Author
Prof. Dr. Shiroh Futaki
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011 Japan
Search for more papers by this authorGraphical Abstract
Break the trap: Inefficient endosomal escape into the cytosol has been a bottleneck in intracellular delivery of biomacromolecules. With appropriate chemical modifications, a cationic amphiphilic peptide, Mastoparan X, became a useful delivery tool that selectively disrupts the endosomal membranes and releases entrapped materials.
Abstract
Endocytosis is an important route for the intracellular delivery of biomacromolecules, wherein their inefficient endosomal escape into the cytosol remains a major barrier. Based on the understanding that endosomal membranes are negatively charged, we focused on the potential of cationic lytic peptides for developing endosomolysis agents to release such entrapped molecules. As such, a venom peptide, Mastoparan X, was employed and redesigned to serve as a delivery tool. Appending a tri-glutamate unit to the N-terminus attenuates the cytotoxicity of Mastoparan X by about 40 fold, while introduction of a NiII-dipicolylamine complex enhances cellular uptake of the peptide by about 17 fold. Using the optimized peptide, various fluorescently labeled macromolecules were successfully delivered to the cytosol, enabling live-cell imaging of acetylated histones.
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