Haruya Sato
Ajinomoto
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Publication
Featured researches published by Haruya Sato.
Biomaterials | 2000
Takuro Niidome; Mamiko Urakawa; Haruya Sato; Yoshiyuki Takahara; Toyoaki Anai; Tomomitsu Hatakayama; Akihiro Wada; Toshiya Hirayama; Haruhiko Aoyagi
To develop a receptor-mediated gene delivery system into hepatoma cells using the cationic alpha-helical peptide as the gene carrier molecule, we modified an alpha-helical peptide, which is known to have transfection abilities into cells, with a multi-antennary ligand containing several galactose residues that provide efficient binding to the asialoglycoprotein receptor. The galactose-modified peptides formed complexes with a plasmid DNA and showed gene transfer abilities into HuH-7 cells, a human hepatoma cell line. The transfection efficiency of the peptide was increased by increasing the number of modified galactose residues on the peptide. Furthermore, considerable inhibition of the transfection efficiency by the addition of asialofetuin, which is a ligand for the asialoglycoprotein receptor, was observed in all galactose-modified peptides. Based on this result, we could confirm that the internalization of the galactose-modified peptides occurred by the receptor-mediated endocytosis pathway. In addition, to understand the transport route of the peptide-DNA complex in the cell, the effects on the transfection efficiencies with several endocytosis inhibitors were examined. As a result, it was suggested that the translocation of the peptide-DNA complex from the endocytic compartments to the cytosol mainly occurred during an early endosome step.
Pharmaceutical Research | 2002
Haruya Sato; Yukio Kato; Eiko Hayashi; Tomoyuki Tabata; Manabu Suzuki; Yoshiyuki Takahara; Yuichi Sugiyama
AbstractPurpose. To demonstrate the utilities of a synthetic low-affinity ligand ((Gal)3) for the asialoglycoprotein receptor (ASGP-R) as a hepatic targeting device for therapeutic cytokines. Methods. The site-specific incorporation of (Gal)3 or a typical high-affinity ligand (GalNAc)3 into IL-2 was catalyzed by microbial transglutaminase. The anti-tumor activities, pharmacokinetic profiles and receptor-mediated endocytosis in hepatocytes of the ligand-IL-2 conjugates were examined in mouse. Results. The (Gal)3 has approximately 50 times lower affinity to ASGP-R than (GalNAc)3. Nevertheless, the antitumor effects were in the order of (Gal)3—IL-2 > unmodified IL-2 > (GalNAc)3—IL-2. The systemic elimination and the hepatic uptake of (GalNAc)3—IL-2 were more rapid than (Gal)3—IL-2. The ratio of the rate constant representing dissociation from the cell-surface receptor (koff) to that representing endocytosis of the ligand (kint) was greater for (Gal)3—IL-2 than (GalNAc)3—IL-2, suggesting that (Gal)3—IL-2 preferably avoids internalization due to its lower affinity to the receptor. The simulation studies demonstrated that (Gal)3—IL-2 was present in the hepatic extracellular space for a longer period than (GalNAc)3 IL-2. Conclusions. The (Gal)3 ligand increases the therapeutic efficacy of IL-2 by enhancing its exposure to the cell-surface. The koff/kint affects the targeting efficacy of the conjugates to ASGP-R.
Bioconjugate Chemistry | 2001
Haruya Sato; Eiko Hayashi; Naoyuki Yamada; Masanobu Yatagai; Yoshiyuki Takahara
Archive | 1997
Yoshiyuki Takahara; Haruya Sato; Eiko Hayashi; Masanobu Yatagai; Manabu Suzuki; Tomoyuki Tabata; Chieko Ejima
Archive | 1995
Haruya Sato; Keiji Yamamoto; Kokichi Suzuki; Masahiro Ikeda; Masahiro Sakagami; Makoto Taniguchi
Bioconjugate Chemistry | 2000
Haruya Sato; Keiji Yamamoto; Eiko Hayashi; Yoshiyuki Takahara
Analytical Biochemistry | 2000
Haruya Sato; Naoyuki Yamada; Nobuhisa Shimba; Yoshiyuki Takahara
Archive | 1995
Haruya Sato; Keiji Yamamoto; Kokichi Suzuki; Masahiro Ikeda; Masahiro Sakagami; Makoto Taniguchi
Archive | 2001
Haruya Sato; Eiko Hayashi; Hideyuki Shirae
Archive | 2002
Haruya Sato; Eiko Hayashi; Hideyuki Shirae