title: Amphipathic short helix-stabilized peptides with cell-membrane penetrating ability.
abstract: We synthesized four types of arginine-based amphipathic nonapeptides, including two homochiral peptides, R-(L-Arg-L-Arg-Aib)3-NH2 (R=6-FAM-β-Ala: FAM-1; R=Ac: Ac-1) and R-(D-Arg-D-Arg-Aib)3-NH2 (R=6-FAM-β-Ala: ent-FAM-1; R=Ac: ent-Ac-1); a heterochiral peptide, R-(L-Arg-D-Arg-Aib)3-NH2 (R=6-FAM-β-Ala: FAM-2; R=Ac: Ac-2); and a racemic mixture of diastereomeric peptides, R-(rac-Arg-rac-Arg-Aib)3-NH2 (R=6-FAM-β-Ala: FAM-3; R=Ac: Ac-3), and then investigated the relationship between their secondary structures and their ability to pass through cell membranes. Peptides 1 and ent-1 formed stable one-handed α-helical structures and were more effective at penetrating HeLa cells than the non-helical peptides 2 and 3.
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, 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: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan. Electronic address: demizu@nihs.go.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Demizu
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Shoda
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan; Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan. Electronic address: masaaki@nihs.go.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kurihara
mesh_terms: D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004705:Endocytosis / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides
keywords: Cell-penetrating peptide; Conformation; DDS carrier; Helical structure