Improvement in the colloidal stability of protein kinase-responsive polyplexes by PEG modification

Akira Tsuchiya, Yuki Naritomi, Satoshi Kushio, Jeong Hun Kang, Masaharu Murata, Makoto Hashizume, Takeshi Mori, Takuro Niidome, Yoshiki Katayama

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

We have reported a disease-cell specific gene expression system that is responsive to intracellular signaling proteins (e.g., protein kinases and proteases) hyperactivated in diseased cells. For this system, cationic peptide-grafted polymers were synthesized for polyplex formation with genes. Here, we modified poly(ethylene glycol) (PEG) to a protein kinase A (PKA)-responsive polymer to improve polyplex stability. PEG modification neutralized the surface charge of the polyplex and successfully increased polyplex stability at physiological conditions. However, PEG modification (PEG contents, 0.6 and 3.3 mol %) showed almost negligible effects on the reactivity of grafted peptides to PKA and the promotion of gene expression responding to PKA activity. Excessive modification of PEG (PEG contents, 6.8 mol %) inhibited polyplex formation. These results indicate that moderate modification of PEG to the enzyme-responsive polymer improves polyplex stability without inhibiting the reaction with enzymes.

元の言語英語
ページ(範囲)1136-1141
ページ数6
ジャーナルJournal of Biomedical Materials Research - Part A
100 A
発行部数5
DOI
出版物ステータス出版済み - 5 1 2012

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Protein Kinases
Polyethylene glycols
Proteins
Cyclic AMP-Dependent Protein Kinases
Polymers
Gene expression
Peptides
Intracellular Signaling Peptides and Proteins
Enzymes
Surface charge
Peptide Hydrolases
Genes

All Science Journal Classification (ASJC) codes

  • Ceramics and Composites
  • Biomaterials
  • Biomedical Engineering
  • Metals and Alloys

これを引用

Improvement in the colloidal stability of protein kinase-responsive polyplexes by PEG modification. / Tsuchiya, Akira; Naritomi, Yuki; Kushio, Satoshi; Kang, Jeong Hun; Murata, Masaharu; Hashizume, Makoto; Mori, Takeshi; Niidome, Takuro; Katayama, Yoshiki.

:: Journal of Biomedical Materials Research - Part A, 巻 100 A, 番号 5, 01.05.2012, p. 1136-1141.

研究成果: ジャーナルへの寄稿記事

Tsuchiya, Akira ; Naritomi, Yuki ; Kushio, Satoshi ; Kang, Jeong Hun ; Murata, Masaharu ; Hashizume, Makoto ; Mori, Takeshi ; Niidome, Takuro ; Katayama, Yoshiki. / Improvement in the colloidal stability of protein kinase-responsive polyplexes by PEG modification. :: Journal of Biomedical Materials Research - Part A. 2012 ; 巻 100 A, 番号 5. pp. 1136-1141.
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abstract = "We have reported a disease-cell specific gene expression system that is responsive to intracellular signaling proteins (e.g., protein kinases and proteases) hyperactivated in diseased cells. For this system, cationic peptide-grafted polymers were synthesized for polyplex formation with genes. Here, we modified poly(ethylene glycol) (PEG) to a protein kinase A (PKA)-responsive polymer to improve polyplex stability. PEG modification neutralized the surface charge of the polyplex and successfully increased polyplex stability at physiological conditions. However, PEG modification (PEG contents, 0.6 and 3.3 mol {\%}) showed almost negligible effects on the reactivity of grafted peptides to PKA and the promotion of gene expression responding to PKA activity. Excessive modification of PEG (PEG contents, 6.8 mol {\%}) inhibited polyplex formation. These results indicate that moderate modification of PEG to the enzyme-responsive polymer improves polyplex stability without inhibiting the reaction with enzymes.",
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AU - Tsuchiya, Akira

AU - Naritomi, Yuki

AU - Kushio, Satoshi

AU - Kang, Jeong Hun

AU - Murata, Masaharu

AU - Hashizume, Makoto

AU - Mori, Takeshi

AU - Niidome, Takuro

AU - Katayama, Yoshiki

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AB - We have reported a disease-cell specific gene expression system that is responsive to intracellular signaling proteins (e.g., protein kinases and proteases) hyperactivated in diseased cells. For this system, cationic peptide-grafted polymers were synthesized for polyplex formation with genes. Here, we modified poly(ethylene glycol) (PEG) to a protein kinase A (PKA)-responsive polymer to improve polyplex stability. PEG modification neutralized the surface charge of the polyplex and successfully increased polyplex stability at physiological conditions. However, PEG modification (PEG contents, 0.6 and 3.3 mol %) showed almost negligible effects on the reactivity of grafted peptides to PKA and the promotion of gene expression responding to PKA activity. Excessive modification of PEG (PEG contents, 6.8 mol %) inhibited polyplex formation. These results indicate that moderate modification of PEG to the enzyme-responsive polymer improves polyplex stability without inhibiting the reaction with enzymes.

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