New strategy for intracellular delivery of biomacropharmaceuticals

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H02497
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kyoto University
• Principal Investigator: Futaki Shiroh 京都大学, 化学研究所, 教授 (50199402)
• Co-Investigator(Renkei-kenkyūsha): TAKEUCHI Toshihide 京都大学, 化学研究所, 助教 (70600120) ; KAWANO Kenichi 京都大学, 化学研究所, 助教 (70732874)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 細胞内送達 / 抗体 / エンドサイトーシス / マクロピノサイトーシス / クモ毒 / 膜傷害性ペプチド

Outline of Final Research Achievements

One of the major obstacles in intracellular targeting using antibodies is their limited release from endosomes into the cytosol. We have developed an approach to deliver biomacromolecules into cells by using endosomolytic peptides derived from the cationic and membrane-lytic spider venom peptide M-lycotoxin. The delivery peptides were developed by introducing a glutamic acid into the hydrophobic face (L17E) to M-lycotoxin, enabling a marked cytosolic liberation of proteins including antibodies from endosomes. The predominant membrane-perturbation mechanism of this peptide is assumed to be the preferential disruption of negatively charged membranes (endosomal membranes) over neutral membranes (plasma membranes), and the endosomolytic peptide promotes the uptake by inducing macropinocytosis.

Free Research Field

生体機能化学