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Fluorescent Mimetics of CMP‐Neu5Ac Are Highly Potent, Cell‐Permeable Polarization Probes of Eukaryotic and Bacterial Sialyltransferases and Inhibit Cellular Sialylation
Author(s) -
Preidl Johannes J.,
Gnanapragassam Vinayaga S.,
Lisurek Michael,
Saupe Jörn,
Horstkorte Rüdiger,
Rademann Jörg
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201400394
Subject(s) - fluorescence , chemistry , cell , microbiology and biotechnology , biophysics , eukaryotic cell , fluorescence anisotropy , bacterial cell structure , biochemistry , bacteria , biology , membrane , genetics , physics , quantum mechanics
Oligosaccharides of the glycolipids and glycoproteins at the outer membranes of human cells carry terminal neuraminic acids, which are responsible for recognition events and adhesion of cells, bacteria, and virus particles. The synthesis of neuraminic acid containing glycosides is accomplished by intracellular sialyl transferases. Therefore, the chemical manipulation of cellular sialylation could be very important to interfere with cancer development, inflammations, and infections. The development and applications of the first nanomolar fluorescent inhibitors of sialyl transferases are described herein. The obtained carbohydrate‐nucleotide mimetics were found to bind all four commercially available and tested eukaryotic and bacterial sialyl transferases in a fluorescence polarization assay. Moreover, it was observed that the anionic mimetics intruded rapidly and efficiently into cells in vesicles and translocated to cellular organelles surrounding the nucleus of CHO cells. The new compounds inhibit cellular sialylation in two cell lines and open new perspectives for investigations of cellular sialylation.