title: The photolytic activity of poly-arginine cell penetrating peptides conjugated to carboxy-tetramethylrhodamine is modulated by arginine residue content and fluorophore conjugation site.
abstract: Upon light irradiation, Fluorophore-cell-penetrating peptide (Fl-CPP) conjugates can disrupt the integrity of biological membranes. This activity can in turn be used to photoinduce the disruption of endocytic organelles and promote the delivery of entrapped macromolecules such as proteins or RNAs into live cells. Recent mechanistic studies have shown that ROS production by the fluorophore and a latent lytic ability of CPPs act in synergy to elicit photolysis. However, how the structure of fluorophore-CPP conjugates impacts this synergistic activity remains unclear. Herein, using red blood cells (RBCs) as a model of biological membranes, we show that the number of arginine residues in a CPP as well as the position of fluorophore with respect to the CPP dramatically affect the photolytic activity of a fluorophore-CPP conjugate. These factors should therefore be considered for the development of effective photoinducible delivery agents.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX.
authors.forename: Nandhini
authors.initials: N
authors.lastname: Muthukrishnan
authors.forename: Stephen
authors.initials: S
authors.lastname: Donovan
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Pellois
mesh_terms: D002463:Cell Membrane Permeability / Q000187:drug effects / Q000528:radiation effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000494:pharmacology; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008027:Light; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D012235:Rhodamines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: C106141:6-carboxytetramethylrhodamine; D057846:Cell-Penetrating Peptides; D005456:Fluorescent Dyes; D010455:Peptides; D017319:Photosensitizing Agents; D012235:Rhodamines; C015462:polyarginine