Sturzu Alexander, Vogel Ulrich, Gharabaghi Alireza, Beck Alexander, Kalbacher Hubert, Echner Hartmut, Heckl Stefan
Department of Neuroradiology; University of Tübingen; Hoppe-Seyler-Str.3; 72076 Tübingen, Germany.
Med Chem. 2009 Jul;5(4):385-91. doi: 10.2174/157340609788681485.
Triiodobenzoic acid (TIBA) represents the core structure of most clinically used contrast agents for computed tomography and other X-ray procedures. To construct an intracellular radiopaque contrast agent, TIBA was coupled to various different positively and negatively charged fluorescein iothiocyanate (FITC)-labelled peptides. TIBA coupled to the SV40 T Antigen nuclear localization sequence (NLS) stained 80% of human glioma cells and caused cell death. This occurred with C- or N-terminal binding of TIBA and with the correct or mutant NLS. No cell death and only small numbers of stained cells (below 3 %) were observed after incubation with NLS conjugates lacking TIBA or after incubation with TIBA-conjugates containing a negatively charged polyglutamic acid stretch. TIBA-conjugates containing the Antennapedia-derived cell-penetrating peptide penetratin were only nuclearly taken up when TIBA and FITC were coupled to lysines outside the 16-amino acid peptide sequence. The study shows that intracellular TIBA may have potential as a chemotherapeutic agent rather than a contrast agent.
三碘苯甲酸（TIBA）是大多数临床上用于计算机断层扫描和其他X射线检查的造影剂的核心结构。为构建一种细胞内不透射线的造影剂，将TIBA与各种不同的带正电荷和负电荷的异硫氰酸荧光素（FITC）标记的肽偶联。与SV40 T抗原核定位序列（NLS）偶联的TIBA使80%的人胶质瘤细胞染色并导致细胞死亡。TIBA的C端或N端结合以及正确或突变的NLS均会出现这种情况。在用缺乏TIBA的NLS缀合物孵育后或在用含有带负电荷的聚谷氨酸片段的TIBA缀合物孵育后，未观察到细胞死亡，仅观察到少量染色细胞（低于3%）。当TIBA和FITC与16个氨基酸肽序列之外的赖氨酸偶联时，含有源自触角足蛋白的细胞穿透肽穿膜肽的TIBA缀合物才会被细胞核摄取。该研究表明，细胞内TIBA可能具有作为化疗药物而非造影剂的潜力。
