Cellular Uptake of Arginine-Rich Cell-Penetrating Peptides and the Contribution of Membrane-Associated Proteoglycans

  • Nakase Ikuhiko
    Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University
  • Kawaguchi Yoshimasa
    Institute for Chemical Research, Kyoto University
  • Nomizu Motoyoshi
    School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
  • Futaki Shiroh
    Institute for Chemical Research, Kyoto University

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  • アルギニンに富む塩基性ペプチドの細胞内への取り込みと膜結合型プロテオグリカンの寄与

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Abstract

Intracellular delivery using cell-penetrating peptides (CPPs) has received considerable interest due to its ease of administration, as well as potential applicability therapeutically. Various bioactive molecules—including peptides/proteins, nucleic acids, liposomes, and nano-particles—that have been conjugated chemically to or have formed complexes with CPPs have been delivered into cells efficiently by the simple addition of these conjugates or complexes to culture media. Although various CPPs with different physicochemical properties have been reported, those rich in arginine are employed most frequently. Membrane-associated proteoglycans such as heparan sulfate proteoglycans play important roles in stimulating the cellular uptake of arginine-rich CPPs and their attached cargoes by concentrating them on cell surfaces via electrostatic interactions between the positive charge on the arginine and negative charges on the glycosaminoglycans. The interaction between arginine-rich CPPs and membrane-associate proteoglycans also induces fluid-phase endocytosis, named macropinocytosis, which facilitates the cellular uptake of arginine-rich CPPs and their cargoes.

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