title: Improvement in the colloidal stability of protein kinase-responsive polyplexes by PEG modification.
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.
authors.affiliation: Graduate School of System Life Sciences, Kyushu University, Nishi-ku, Fukuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Yuki
authors.initials: Y
authors.lastname: Naritomi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kushio
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kang
authors.forename: Masaharu
authors.initials: M
authors.lastname: Murata
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashizume
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mori
authors.forename: Takuro
authors.initials: T
authors.lastname: Niidome
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000595:Amino Acid Sequence; D003102:Colloids / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D008027:Light; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011494:Protein Kinases / Q000378:metabolism*; D012542:Scattering, Radiation
chemical_list: D003102:Colloids; D010455:Peptides; D011092:Polyethylene Glycols; D004247:DNA; D008156:Luciferases; D011494:Protein Kinases