Abstract
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.
Keywords: 2,3,5-triiodobenzoic acid, NLS, cell nucleus, FITC, transmembrane transport, glioma, penetratin, polyglutamic acid
Medicinal Chemistry
Title: Cell Nucleus Directed 2,3,5-triiodobenzoic Acid Conjugates
Volume: 5 Issue: 4
Author(s): Alexander Sturzu, Ulrich Vogel, Alireza Gharabaghi, Alexander Beck, Hubert Kalbacher, Hartmut Echner and Stefan Heckl
Affiliation:
Keywords: 2,3,5-triiodobenzoic acid, NLS, cell nucleus, FITC, transmembrane transport, glioma, penetratin, polyglutamic acid
Abstract: 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.
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Sturzu Alexander, Vogel Ulrich, Gharabaghi Alireza, Beck Alexander, Kalbacher Hubert, Echner Hartmut and Heckl Stefan, Cell Nucleus Directed 2,3,5-triiodobenzoic Acid Conjugates, Medicinal Chemistry 2009; 5 (4) . https://dx.doi.org/10.2174/157340609788681485
DOI https://dx.doi.org/10.2174/157340609788681485 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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