A "ready-to-use" fluorescent-labelled-cysteine-TBTP (4-thiobutyltriphenylphosphonium) synthon to investigate the delivery of non-permeable PNA (peptide nucleic acids)-based compounds to cells |
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Authors: | Mehiri Mohamed Caldarelli Sergio Di Giorgio Audrey Barouillet Thibault Doglio Alain Condom Roger Patino Nadia |
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Institution: | Laboratoire de Chimie des Molécules Bioactives et des Ar?mes UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France. |
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Abstract: | This paper reports: (i) the facile synthesis of a cysteine synthon incorporating both a fluorescent group and a triphenylphosphonium derivative (TBTP) via the formation of a disulphide bond, which can subsequently undergo facile intracellular scission, (ii) the direct conjugation of this synthon to a non-permeable drug, (a cyclic PNA (peptide nucleic acid)-based compound has been chosen as a model), and (iii) that this conjugation enables the efficient homogenous delivery of the otherwise non-permeable cyclic PNA into the cytoplasm of cells, as demonstrated by fluorescence microscopy. Our results indicate that this fluorescent-labelled cysteine-TBTP synthon can provide a very useful tool for exploring the cellular uptake of a large range of molecules of biological interest, containing only a single reactive function. The preparation of an activated TBTP derivative is also described and this procedure could be widely used to introduce a TBTP cation to any thio-containing molecule. |
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Keywords: | PNA cellular delivery Lipophilic triphenylphosphonium cation Fluorescence microscopy |
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