http://www.cnr.it/ontology/cnr/individuo/prodotto/ID17771

Charged Hexosaminides as New Substrates for beta-N-Acetylhexosaminidase-Catalyzed Synthesis of Immunomodulatory Disaccharides (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Charged Hexosaminides as New Substrates for beta-N-Acetylhexosaminidase-Catalyzed Synthesis of Immunomodulatory Disaccharides (Articolo in rivista) (literal)

Anno

2011-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1002/adsc.201100371 (literal)

Alternative label

Bojarovà P., Slamovà K., Krened K., Gazak R., Kulik N., Ettrich R., Pelantovà H., Kuzma M., Riva S., Adàmek D., Bezouska K., Kren V. (2011)
Charged Hexosaminides as New Substrates for beta-N-Acetylhexosaminidase-Catalyzed Synthesis of Immunomodulatory Disaccharides
in Advanced synthesis & catalysis (Print)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Bojarovà P., Slamovà K., Krened K., Gazak R., Kulik N., Ettrich R., Pelantovà H., Kuzma M., Riva S., Adàmek D., Bezouska K., Kren V. (literal)

Pagina inizio

2409 (literal)

Pagina fine

2420 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

353 (literal)

Rivista

Advanced synthesis & catalysis (Rivista)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Institute of Microbiology, Academy of Sciences of the Czech Republic, Víde?ská 1083, CZ-142 20 Praha 4, Czech Republic, Fax: (+420)-296-442-509; phone: (+420)-296-442-510,;Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technická 5, CZ-16628 Praha 6, Czech Republic; Department of Structure and Function of Proteins, Institute of Nanobiology and Structural Biology of GCRC, Zámek 136, CZ-373 33 Nové Hrady, Czech Republic; Istituto di Chimica del Riconoscimento Molecolare, CNR, Via Mario Bianco 9, I-20131 Milano, Italy;Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 8, CZ-128 40 Praha 2, Czech Republic (literal)

Titolo

Charged Hexosaminides as New Substrates for beta-N-Acetylhexosaminidase-Catalyzed Synthesis of Immunomodulatory Disaccharides (literal)

Abstract

This work is a structure-activity relationship study that investigates the influence of the nature and amount of negative charge in carbohydrate substrates on the affinity of ?-N-acetylhexosaminidases, and on the stimulation of natural killer cells. It describes synthetic procedures yielding novel glycosides that are useful in immunoactivation. Specifically, we present a thorough study on the ability of six C-6 modified ?-N-acetylhexosaminides (aldehyde, uronate, 6-O-sulfate, 6-O-phosphate) to serve as substrates for cleavage and glycosylation by a library of ?-N-acetylhexosaminidases from various sources. Four novel disaccharides with one or two (negatively) charged groups were prepared in synthetic reactions in good yields. Surprisingly, the 6-O-phosphorylated substrate, although cleaved by a number of enzymes from the series, worked neither as a donor nor as an acceptor in transglycosylation reactions. The results of wet experiments were supported by molecular modeling of substrates in the active site of two representative enzymes from the screening. All ten prepared compounds were examined in terms of their immunoactivity, namely as ligands of two activation receptors of natural killer (NK) cells, NKR-P1 and CD69, both with isolated proteins and whole cells. Sulfated disaccharides in particular acted as very efficient protectants of NK cells against activation-induced apoptosis, and as stimulants of the natural killing of resistant tumor cells, which makes them good candidates for potential clinical use in cancer treatment. (literal)

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