Penas Cristina, Sánchez Mateo I, Guerra-Varela Jorge, Sanchez Laura, Vázquez M Eugenio, Mascareñas José L
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.
Departmento de Xenética, Facultade de Veterinaria, Universidade de Santiago de Compostela, Av. Carballo Calero s/n, 27002, Lugo, Spain.
Chembiochem. 2016 Jan 1;17(1):37-41. doi: 10.1002/cbic.201500455. Epub 2015 Nov 27.
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.
我们合成了DNA结合剂（双苯甲脒、吖啶和噻唑橙）的八聚精氨酸缀合物，并证明通过光不稳定接头连接一个（带负电荷的）寡聚谷氨酸尾巴可以抑制它们与DNA的结合及细胞内化。紫外线照射会释放出母体缀合物，从而恢复细胞内化和生物活性。对斑马鱼胚胎的检测证明了这种前药策略在控制体内细胞毒性方面的潜力。
