Cell nucleus directed 2,3,5-triiodobenzoic acid conjugates

Med Chem. 2009 Jul;5(4):385-91. doi: 10.2174/157340609788681485.

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.

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology
  • Biological Transport
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Fluorescein-5-isothiocyanate / metabolism
  • Humans
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / metabolism
  • Staining and Labeling
  • Triiodobenzoic Acids / chemistry*
  • Triiodobenzoic Acids / metabolism*
  • Triiodobenzoic Acids / pharmacology

Substances

  • Antineoplastic Agents
  • Peptides
  • Triiodobenzoic Acids
  • 2,3,5-triiodobenzoic acid
  • Fluorescein-5-isothiocyanate