Transport of Nucleoside Triphosphates into Cells by Artificial Molecular Transporters

0492284 - ÚOCHB 2019 RIV DE eng J - Journal Article
Zawada, Zbigniew - Tatar, Ameneh - Mocilac, Pavle - Buděšínský, Miloš - Kraus, Tomáš
Transport of Nucleoside Triphosphates into Cells by Artificial Molecular Transporters.
Angewandte Chemie - International Edition. Roč. 57, č. 31 (2018), s. 9891-9895. ISSN 1433-7851. E-ISSN 1521-3773
R&D Projects: GA ČR(CZ) GA17-14791S
Institutional support: RVO:61388963
Keywords : anion transporters * nucleotide triphosphates * cell-penetrating peptides * cyclodextrins * DNA labelling
OECD category: Organic chemistry
Impact factor: 12.257, year: 2018

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.
Permanent Link: http://hdl.handle.net/11104/0285807