Transport of Nucleoside Triphosphates into Cells by Artificial Molecular Transporters

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...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2018-07, Vol.57 (31), p.9891-9895
Main Authors: Zawada, Zbigniew, Tatar, Ameneh, Mocilac, Pavle, Buděšínský, Miloš, Kraus, Tomáš
Format: Article
Language:English
Subjects:
anion transporters
Anions
Biological Transport
Cell Line, Tumor
Cell membranes
cell-penetrating peptides
Coordination compounds
cyclodextrins
Deoxyribonucleic acid
DNA
DNA labelling
Eukaryotic Cells - chemistry
Eukaryotic Cells - metabolism
Humans
Membranes
Metabolites
Molecular chains
Molecular Structure
Nuclear transport
Nucleoli
Nucleoside triphosphates
Nucleosides
nucleotide triphosphates
Nucleotides - chemistry
Nucleotides - metabolism
Optical Imaging
Organic chemistry
Polyphosphates - chemistry
Polyphosphates - metabolism
Precursors
Transport
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Summary: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. Let the right one in: Nucleoside triphosphates (NTPs) can be directly transported into eukaryotic cells and bacteria by the action of designed synthetic nucleoside triphosphate transporters (SNTTs). The transport of NTPs proceeds rapidly—within seconds to minutes—and selectively even in the presence of other organic anions. This operationally simple and efficient means to transport fluorescently labelled NTPs into cells can be used for the metabolic labeling of DNA in live cells.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201801306