title: A Helix-Stabilized Cell-Penetrating Peptide as an Intracellular Delivery Tool.
abstract: Two types of cationic cyclic α,α-disubstituted α-amino acids: ApiC2NH2 (which possesses a lysine mimic side chain) and Api(C2Gu) (which possesses an arginine mimic side chain), were developed. These amino acids were incorporated into an arginine-based peptide sequence [(L-Arg-L-Arg-dAA)3: dAA=ApiC2NH2 or Api(C2Gu)], and the relationship between the secondary structures of the resulting peptides and their ability to pass through cell membranes was investigated. The peptide containing Api(C2Gu) formed a stable α-helical structure and was more effective at penetrating cells than the nonhelical Arg nonapeptide (R9). Furthermore, the peptide was able to deliver plasmid DNA into various types of cells in a highly efficient manner.
authors.affiliation: National Institute of Health Sciences, Setagaya, Tokyo, 158-8501, Japan.|Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.affiliation: National Institute of Health Sciences, Setagaya, Tokyo, 158-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Misawa
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: National Institute of Health Sciences, Setagaya, Tokyo, 158-8501, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hattori
authors.affiliation: National Institute of Health Sciences, Setagaya, Tokyo, 158-8501, Japan.
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
authors.affiliation: National Institute of Health Sciences, Setagaya, Tokyo, 158-8501, Japan. demizu@nihs.go.jp.|Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan. demizu@nihs.go.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurihara
authors.affiliation: National Institute of Health Sciences, Setagaya, Tokyo, 158-8501, Japan. masaaki@nihs.go.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Demizu
mesh_terms: D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D010957:Plasmids / Q000737:chemistry*
chemical_list: D057846:Cell-Penetrating Peptides
keywords: cell-penetrating peptides; helical structure; non-proteinogenic amino acids; plasmid DNA delivery