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.
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.
Mehiri
Mohamed
M
Laboratoire de Chimie des Molécules Bioactives et des Arômes UMR-CNRS 6001, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France.
Caldarelli
Sergio
S
Di Giorgio
Audrey
A
Barouillet
Thibault
T
Doglio
Alain
A
Condom
Roger
R
Patino
Nadia
N
D002463:Cell Membrane Permeability; D002477:Cells; D003545:Cysteine / Q000737:chemistry; D003593:Cytoplasm / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D020135:Peptide Nucleic Acids / Q000008:administration & dosage*
D004337:Drug Carriers; D005456:Fluorescent Dyes; D009943:Organophosphorus Compounds; D020135:Peptide Nucleic Acids; C095693:thiobutyltriphenylphosphonium; D003545:Cysteine