Light-Controlled Cellular Internalization and Cytotoxicity of Nucleic Acid-Binding Agents: Studies in Vitro and in Zebrafish Embryos

This is the peer reviewed version of the following article: C. Penas, M. I. Sánchez, J. Guerra-Varela, L. Sanchez, M. E. Vázquez, J. L. Mascareñas, ChemBioChem 2016, 17, 37-41, which has been published in final form at https://doi.org/10.1002/cbic.201500455. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsWe 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 cytotoxicityWe are thankful for the support given by the Spanish grants SAF2013–41943‐R, CTQ2012–31341 and CTQ2013–49317‐EXP, the Xunta de Galicia GRC2013–041, the ERDF and the European Research Council (Advanced Grant 340055). C.P. and M.I.S. thank the Spanish MCINN for their PhD fellowshipsS