title: Light-Controlled Cellular Internalization and Cytotoxicity of Nucleic Acid-Binding Agents: Studies in Vitro and in Zebrafish Embryos.
abstract: We synthesized octa-arginine conjugates of DNA-binding agents (bisbenzamidine, acridine and Thiazole Orange) and demonstrated that their DNA binding and cell internalization can be inhibited by appending a (negatively charged) oligoglutamic tail through a photolabile linker. UV irradiation released the parent conjugates, thus restoring cell internalization and biological activity. Assays with zebrafish embryos demonstrates the potential of this prodrug strategy for controlling in vivo cytotoxicity.
authors.affiliation: Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais, Moleculares (CIQUS), Universidade de Santiago de Compostela, Jenaro de la Fuente s/n, Campus Vida, 15782, Santiago de Compostela, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Penas
authors.affiliation: Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais, Moleculares (CIQUS), Universidade de Santiago de Compostela, Jenaro de la Fuente s/n, Campus Vida, 15782, Santiago de Compostela, Spain.
authors.forename: Mateo I
authors.initials: MI
authors.lastname: Sánchez
authors.affiliation: Departmento de Xenética, Facultade de Veterinaria, Universidade de Santiago de Compostela, Av. Carballo Calero s/n, 27002, Lugo, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Guerra-Varela
authors.affiliation: Departmento de Xenética, Facultade de Veterinaria, Universidade de Santiago de Compostela, Av. Carballo Calero s/n, 27002, Lugo, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sanchez
authors.affiliation: Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais, Moleculares (CIQUS), Universidade de Santiago de Compostela, Jenaro de la Fuente s/n, Campus Vida, 15782, Santiago de Compostela, Spain. eugenio.vazquez@usc.es.
authors.forename: M Eugenio
authors.initials: ME
authors.lastname: Vázquez
authors.affiliation: Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais, Moleculares (CIQUS), Universidade de Santiago de Compostela, Jenaro de la Fuente s/n, Campus Vida, 15782, Santiago de Compostela, Spain. joseluis.mascarenas@usc.es.
authors.forename: José L
authors.initials: JL
authors.lastname: Mascareñas
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000737:chemistry* / Q000494:pharmacology; D001550:Benzamidines / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002477:Cells / Q000187:drug effects / Q000378:metabolism*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays; D015027:Zebrafish / Q000196:embryology
chemical_list: D000166:Acridines; D001550:Benzamidines; D052160:Benzothiazoles; D011355:Prodrugs; D011804:Quinolines; D005973:Glutamine; C051000:thiazole orange; D004247:DNA; D001120:Arginine; C032157:benzamidine
keywords: DNA recognition; caged compounds; fluorescent probes; peptides; supramolecular chemistry