title: Cell-penetrating helical peptides having l-arginines and five-membered ring α,α-disubstituted α-amino acids.
abstract: Cell-penetrating peptides are powerful tools in the delivery of drugs, proteins, and nucleic acids into cells; therefore, focus has recently been placed on their development. In this study, we synthesized seven types of peptides possessing three l-arginines (l-Arg) and six l-leucines (l-Leu) and/or 1-aminocyclopentane-1-carboxylic acids (Ac5c), and investigated their secondary structures and cell-penetrating abilities. The peptide composed of an equal number of l-Arg, l-Leu, and Ac5c formed 310/α-helical structures in TFE solution and exhibited the highest cell-penetrating ability of all the peptides examined. Additional cellular uptake studies revealed that the incorporation of Ac5c into peptides led to improved tolerability against serum. The results of the present study will help in the design of novel cell-penetrating peptides.
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University , 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Kato
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
authors.forename: Masakazu
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry* / Q000493:pharmacokinetics; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D003515:Cycloleucine / Q000737:chemistry* / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000737:chemistry* / Q000493:pharmacokinetics; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D057846:Cell-Penetrating Peptides; D003515:Cycloleucine; D001120:Arginine; D007930:Leucine