Glycan‐Specific Metabolic Oligosaccharide Engineering of C7‐Substituted Sialic Acids

Möller, Heinz; Böhrsch, Verena; Bentrop, Joachim; Bender, Judith; Hinderlich, Stephan; Hackenberger, Christian P. R.

doi:10.1002/anie.201108809

Cited by 44 publications

(36 citation statements)

References 31 publications

(19 reference statements)

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“…Metabolischer Einbau von Aziden in die Sialinsäuren der Zelloberfläche mittels Ac 4 ManNAz [5,6,19] [17,18,[20][21][22][23][24] Der bioorthogonale Marker Bicyclo-[6.1.0]nonin (BCN) wurde wegen seiner überlegenen Reaktivität und Selektivität bei der Markierung von Glykanen gewählt. [25] Der Einbau von Fluorescein ermçglicht schließ-lich eine alternative Detektion zur Verifizierung der Selektivität und zur Quantifizierung der Biosensor-Aufnahme.…”

Section: Angewandte Zuschriftenunclassified

Xenon‐MRT an lebenden Zellen mit Hyper‐CEST‐Biosensoren für metabolisch markierte Glykane an der Zelloberfläche

et al. 2015

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Das Targeting von metabolisch markierten Glykanen mit herkçmmlichen MRT-Kontrastmitteln erschien bislang als nicht realisierbar. Hier erweitern wir die Anwendungen von Xenon-Hyper-CEST-Biosensoren in Zellen und präsentieren damit die erste erfolgreiche molekulare Bildgebung dieser Glykane mittels MRT. Hyper-CEST-Biosensoren sind eine neue Klasse von MRT-Kontrastmitteln mit sehr hoher Empfindlichkeit. Darauf basierend wurde ein multimodaler Biosensor für sowohl Fluoreszenz-als auch Xenon-MRT-Detektion entwickelt, der selektiv mit metabolisch markierten Sialinsäuren durch bioorthogonale Chemie verknüpft wurde. Die Verwendung eines kürzlich entwickelten Bioreaktors zur Untersuchung lebender Zellen ermçglicht somit den Nachweis von Zelloberflächenglykanen mittels Xenon-MRT bei nanomolaren Konzentrationen.

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Section: Angewandte Zuschriftenunclassified

Xenon‐MRT an lebenden Zellen mit Hyper‐CEST‐Biosensoren für metabolisch markierte Glykane an der Zelloberfläche

et al. 2015

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“…168 In addition to metabolic labelling of sialic acid-containing glycans, 169,170 other sectors of the glycome can be metabolically labelled using azido analogs of N -acetylglucosamine (β- O -GlcNAcylated proteins), 171 N -acetylgalactosamine (mucin-type O-linked glycans and β- O -GlcNAcylated proteins), 172,173 and fucose (fucosylated glycans) (Fig. 7B).…”

Section: Chemical Reporter Strategymentioning

confidence: 99%

Imaging beyond the proteome

Chang

Bertozzi

2012

Chem. Commun.

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Imaging technologies developed in the early 20th century achieved contrast solely by relying on macroscopic and morphological differences between the tissues of interest and the surrounding tissues. Since then, there has been a movement toward imaging at the cellular and molecular level in order to visualize biological processes. This rapidly growing field is known as molecular imaging. In the last decade, many methodologies for imaging proteins have emerged. However, most of these approaches cannot be extended to imaging beyond the proteome. Here, we highlight some of the recently developed technologies that enable imaging of non-proteinaceous molecules in the cell: lipids, signalling molecules, inorganic ions, glycans, nucleic acids, small-molecule metabolites, and protein post-translational modifications such as phosphorylation and methylation.

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“…24 Recently, peracetylated N -acetyl-4-azido-4-deoxymannosamine (peracetylated 4-azido-ManNAc) was used successfully for metabolic engineering of mammalian cell surface glycoproteins with 7-azido-Neu5Ac, indicating the tolerance of 4-azido-modified ManNAc by mammalian cellular enzymes involved in sialic acid biosynthesis, activation, and transfer to glycoproteins. 25 Unlike metabolic engineering of cultured mammalian cells with peracetylated N -azidoacetylmannosamine (peracetylated ManNAz) which introduced Neu5Az to both N- and O-glycans on cell surface glycoproteins, incubating UDP- N -acetylglucosamine 2-epimerase/ManNAc kinase (GNE) deficient HEK293 cells with peracetylated 4-azido-ManNAc introduced 7-azido-Neu5Ac only to the O-glycans of cell surface glycoproteins. Success in labelling O-glycosylated proteins in live zebrafish embryos during development was also achieved.…”

Section: Introductionmentioning

confidence: 99%

“…Success in labelling O-glycosylated proteins in live zebrafish embryos during development was also achieved. 25 Nevertheless, there are only a few reports on the chemical synthesis of sialosides containing 7-deoxy Neu5Ac 26,27 and testing their binding to sialoside-binding proteins. 27 Enzymatic synthesis of sialosides containing C7-modified sialic acid and their applications in investigating sialidase activities have not been achieved.…”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic synthesis of sialosides containing C7-modified sialic acids and their application in sialidase substrate specificity studies

Khedri

Muthana

et al. 2014

Carbohydrate Research

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Modification at the glycerol side chain of sialic acid in sialosides modulate their recognition by sialic acid-binding proteins and sialidases. However, limited work has been focused on the synthesis and functional studies of sialosides with C7-modified sialic acids. Here we report chemical synthesis of C4-modified ManNAc and mannose and their application as sialic acid precursors in a highly efficient one-pot three-enzyme system for chemoenzymatic synthesis of α2–3- and α2–6-linked sialyl para-nitrophenyl galactosides in which the C7-hydroxyl group in sialic acid (N-acetylneuraminic acid, Neu5Ac, or 2-keto-3-deoxynonulosonic acid, Kdn) was systematically substituted by -F, -OMe, -H, and -N3 groups. Substrate specificity study of bacterial and human sialidases using the obtained sialoside library containing C7-modified sialic acids showed that sialosides containing C7-deoxy Neu5Ac were selective substrates for all bacterial sialidases tested but not for human NEU2. The information obtained from sialidase substrate specificity can be used to guide the design of new inhibitors that are selective against bacterial sialidases.

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Glycan‐Specific Metabolic Oligosaccharide Engineering of C7‐Substituted Sialic Acids

Cited by 44 publications

References 31 publications

Xenon‐MRT an lebenden Zellen mit Hyper‐CEST‐Biosensoren für metabolisch markierte Glykane an der Zelloberfläche

Xenon‐MRT an lebenden Zellen mit Hyper‐CEST‐Biosensoren für metabolisch markierte Glykane an der Zelloberfläche

Imaging beyond the proteome

Chemoenzymatic synthesis of sialosides containing C7-modified sialic acids and their application in sialidase substrate specificity studies

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