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Transport of Nucleoside Triphosphates into Cells by Artificial Molecular Transporters
Author(s) -
Zawada Zbigniew,
Tatar Ameneh,
Mocilac Pavle,
Buděšínský Miloš,
Kraus Tomáš
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201801306
Subject(s) - nucleoside , chemistry , nucleoside transporter , biochemistry , membrane transport , membrane , intracellular , nucleoside triphosphate , transporter , biophysics , nucleotide , biology , gene
Chemically modified nucleoside triphosphates (NTPs) are widely exploited as unnatural metabolites in chemical biology and medicinal chemistry. Because anionic NTPs do not permeate cell membranes, their corresponding neutral precursors are employed in cell‐based assays. These precursors become active metabolites after enzymatic conversion, which often proceeds insufficiently. Here we show that metabolically‐active NTPs can be directly transported into eukaryotic cells and bacteria by the action of designed synthetic nucleoside triphosphate transporters (SNTTs). The transporter is composed of a receptor, which forms a non‐covalent complex with a triphosphate anion, and a cell‐penetrating agent, which translocates the complex across the plasma membrane. NTP is then released from the complex in the intracellular milieu and accumulates in nuclei and nucleoli in high concentration. The transport of NTPs proceeds rapidly (seconds to minutes) and selectively even in the presence of other organic anions. We demonstrate that this operationally simple and efficient means of transport of fluorescently labelled NTPs into cells can be used for metabolic labeling of DNA in live cells.