conjugation to the cell-penetrating peptide tat potentiates the photodynamic effect of carboxytetramethylrhodamine结合到cell-penetrating肽答强化carboxytetramethylrhodamine的光动力效应.pdfVIP

Conjugation to the Cell-Penetrating Peptide TAT Potentiates the Photodynamic Effect of Carboxytetramethylrhodamine 1. 1. 1 1 Divyamani Srinivasan , Nandhini Muthukrishnan , Gregory A. Johnson , Alfredo Erazo-Oliveras , 2 2 1 Jongdoo Lim , Eric E. Simanek , Jean-Philippe Pellois * 1 Department of Biochemistry and Biophysics, Texas AM University, College Station, Texas, United States of America, 2 Department of Chemistry, Texas AM University, College Station, Texas, United States of America Abstract Background: Cell-penetrating peptides (CPPs) can transport macromolecular cargos into live cells. However, the cellular delivery efficiency of these reagents is often suboptimal because CPP-cargo conjugates typically remain trapped inside endosomes. Interestingly, irradiation of fluorescently labeled CPPs with light increases the release of the peptide and its cargos into the cytosol. However, the mechanism of this phenomenon is not clear. Here we investigate the molecular basis of the photo-induced endosomolytic activity of the prototypical CPPs TAT labeled to the fluorophore 5(6)- carboxytetramethylrhodamine (TMR). Methodology/Principal Findings: We report that TMR-TAT acts as a photosensitizer that can destroy membranes. TMR-TAT escapes from endosomes after exposure to moderate light doses. However, this is also accompanied by loss of plasma membrane integrity, membrane blebbing, and cell-death. In addition, the peptide causes the destruction of cells when applied extracellularly and also triggers the photohemolysis of red blood ce