Cell nucleus directed 2,3,5-triiodobenzoic acid conjugates.
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.
Sturzu
Alexander
A
Department of Neuroradiology; University of Tübingen; Hoppe-Seyler-Str.3; 72076 Tübingen, Germany.
Vogel
Ulrich
U
Gharabaghi
Alireza
A
Beck
Alexander
A
Kalbacher
Hubert
H
Echner
Hartmut
H
Heckl
Stefan
S
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D013194:Staining and Labeling; D014283:Triiodobenzoic Acids / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
D000970:Antineoplastic Agents; D010455:Peptides; D014283:Triiodobenzoic Acids; C052968:2,3,5-triiodobenzoic acid; D016650:Fluorescein-5-isothiocyanate