title: Synergy between cell-penetrating peptides and singlet oxygen generators leads to efficient photolysis of membranes.
abstract: Cell-penetrating peptides such as TAT or R9 labeled with small organic fluorophores can lyse endosomes upon light irradiation. The photoendosomolytic activity of these compounds can in turn be used to deliver proteins and nucleic acids to the cytosol of live cells with spatial and temporal control. In this report, we examine the mechanisms by which such fluorescent peptides exert a photolytic activity using red blood cells as a membrane model. We show that the peptides TAT and R9 labeled with tetramethylrhodamine photolyze red blood cells by promoting the formation of singlet oxygen in the vicinity of the cells' membranes. In addition, unlabeled TAT and R9 accelerate the photolytic activity of the membrane-bound photosensitizer Rose bengal in trans, suggesting that the cell-penetrating peptides participate in the destabilization of photo-oxidized membranes. Peptides and singlet oxygen generators therefore act in synergy to destroy membranes upon irradiation.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.
authors.forename: Nandhini
authors.initials: N
authors.lastname: Muthukrishnan
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Johnson
authors.forename: Alfredo
authors.initials: A
authors.lastname: Erazo-Oliveras
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Pellois
mesh_terms: D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000528:radiation effects; D057846:Cell-Penetrating Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D005456:Fluorescent Dyes; D015696:Gene Products, tat / Q000138:chemical synthesis / Q000494:pharmacology*; D006461:Hemolysis; D006801:Humans; D008027:Light; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D012235:Rhodamines; D012395:Rose Bengal / Q000737:chemistry / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000737:chemistry
chemical_list: D057846:Cell-Penetrating Peptides; D005456:Fluorescent Dyes; D015696:Gene Products, tat; D009842:Oligopeptides; D017319:Photosensitizing Agents; D012235:Rhodamines; D026082:Singlet Oxygen; D012395:Rose Bengal; C005358:tetramethylrhodamine