title: Efficient delivery of cyclic peptides into mammalian cells with short sequence motifs.
abstract: Cyclic peptides hold great potential as therapeutic agents and research tools, but their broad application has been limited by poor membrane permeability. Here, we report a potentially general approach for intracellular delivery of cyclic peptides. Short peptide motifs rich in arginine and hydrophobic residues (e.g., FΦRRRR, where Φ is l-2-naphthylalanine), when embedded into small- to medium-sized cyclic peptides (7-13 amino acids), bound to the plasma membrane of mammalian cultured cells and were subsequently internalized by the cells. Confocal microscopy and a newly developed peptide internalization assay demonstrated that cyclic peptides containing these transporter motifs were translocated into the cytoplasm and nucleus at efficiencies 2-5-fold higher than that of nonaarginine (R(9)). Furthermore, incorporation of the FΦRRRR motif into a cyclic peptide containing a phosphocoumaryl aminopropionic acid (pCAP) residue generated a cell permeable, fluorogenic probe for detecting intracellular protein tyrosine phosphatase activities.
authors.affiliation: Department of Chemistry and Biochemistry and Ohio State Biochemistry Program, The Ohio State University , 100 West 18th Avenue, Columbus, Ohio 43210, USA.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Qian
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Yu-Yu
authors.initials: YY
authors.lastname: Liu
authors.forename: Roger
authors.initials: R
authors.lastname: Briesewitz
authors.forename: Amy M
authors.initials: AM
authors.lastname: Barrios
authors.forename: Sissy M
authors.initials: SM
authors.lastname: Jhiang
authors.forename: Dehua
authors.initials: D
authors.lastname: Pei
mesh_terms: D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D010456:Peptides, Cyclic