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The Fluorinated and Chlorinated Nuclear Localization Sequence of the SV 40 T Antigen
Author(s) -
Sturzu Alexander,
Heckl Stefan
Publication year - 2009
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2008.00736.x
Subject(s) - nuclear localization sequence , nls , cytoplasm , antigen , nuclear transport , staining , sequence (biology) , peptide sequence , programmed cell death , microbiology and biotechnology , cell nucleus , biology , fluorescein , nuclear pore , conjugate , biochemistry , chemistry , fluorescence , apoptosis , gene , immunology , genetics , physics , quantum mechanics , mathematical analysis , mathematics
Nuclear uptake of the simian virus (SV) 40 T antigen is triggered by a specific nuclear localization sequence. However, such a nuclear localization sequence is only poorly taken up by the cytoplasm of cells when administered to the culture medium. Our aim was to improve the cytoplasmic uptake of the SV 40 T antigen nuclear localization sequence. Consequently, we synthesized novel fluorescein isothiocyanate‐labelled conjugates containing the nuclear localization sequences of the SV 40 T antigen and either trichlorobenzoic or trifluorobenzoic acid. Applied at 260 μ m such halogenated NLS conjugates were nuclearly taken up by 75–85% of U373 and LN18 glioma cells and resulted in cell death. Nuclear staining and cell death were also found at lower concentrations (130 and 65 μ m ) of halogenated nuclear localization sequence conjugates. By contrast only a low cellular staining rate and no cell death could be observed after co‐incubation with a trichlorobenzoic acid or trifluorobenzoic acid‐lacking nuclear localization sequence conjugate and free, unbound trichlorobenzoic acid or trifluorobenzoic acid at the high concentration (260 μ m ). Such small non‐radioactive fluorinated and chlorinated nuclear localization sequences may be used as important components for future antiglioma drug development.