Fluorescent mimetics of CMP-Neu5Ac are highly potent, cell-permeable polarization probes of eukaryotic and bacterial sialyltransferases and inhibit cellular sialylation.
Angew Chem Int Ed Engl
; 53(22): 5700-5, 2014 May 26.
Article
em En
| MEDLINE
| ID: mdl-24737687
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Ácidos Siálicos
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Sialiltransferases
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Monofosfato de Citidina
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Inibidores Enzimáticos
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Corantes Fluorescentes
Limite:
Animals
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2014
Tipo de documento:
Article