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

Bioorg Chem. 2007 Aug;35(4):313-26. doi: 10.1016/j.bioorg.2007.01.002. Epub 2007 Mar 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane Permeability
  • Cells
  • Cysteine / chemistry
  • Cytoplasm / metabolism
  • Drug Carriers / chemical synthesis*
  • Drug Carriers / pharmacokinetics*
  • Fluorescent Dyes
  • HeLa Cells
  • Humans
  • Microscopy, Fluorescence
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / pharmacokinetics*
  • Peptide Nucleic Acids / administration & dosage*

Substances

  • Drug Carriers
  • Fluorescent Dyes
  • Organophosphorus Compounds
  • Peptide Nucleic Acids
  • thiobutyltriphenylphosphonium
  • Cysteine