Preparation and Biological Activities of a Bivalent Poly(Ethylene Glycol) Hybrid Containing an Active Site and Its Synergistic Site of Fibronectin.

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  • Susuki Yuichi
    Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University
  • Hojo Keiko
    Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University
  • Okazaki Ikuko
    Graduate School of Environmental Earth Science, Hokkaido University
  • Kamata Haruhiko
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University
  • Sasaki Masahiko
    Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University
  • Maeda Mitsuko
    Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University
  • Nomizu Motoyoshi
    Graduate School of Environmental Earth Science, Hokkaido University
  • Yamamoto Yoko
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University
  • Nakagawa Shinsaku
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University
  • Mayumi Tadanori
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University
  • Kawasaki Koichi
    Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University

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説明

A bivalent poly(ethylene glycol) or PEG hybrid of fibronectin-related peptides was prepared. An active site peptide (RGD) and its synergistic site peptide (PHSRN) of fibronectin were conjugated with an amino acid-type PEG (aaPEG) to form PHSRN–aaPEG–RGD. A moderate spatial array between RGD and PHSRN in fibronectin may be required for synergic activity. The bivalent hybrid exhibited potent cell spreading activity and exhibited potent anti-metastatic activity in a model of experimental metastasis with B16–BL6 cells in mice. PEG may serve as a spacer for maintaining the desired spatial array.

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