Light‐controlled cellular internalization and cytotoxicity of nucleic acid‐binding agents. Studies in vitro and in zebrafish embryos

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.