- Start of Action – 26/10/2001; End of Action – 25/04/2007
Novel methods for enzymatic synthesis of bioactive glycosides
New enzymes for synthesis of oligoglycosides will be screened and characterized, especially a/b N-acetylmannosaminidase which is not known yet, enzyme library will be created. Novel methods for enzymatic synthesis of bioactive glycosides will be developed using complementary approaches, e.g., biphasic systems, cosolvents, ionic liquids, high salt concentrations. New reaction conditions will be tested in enzymatic glycosylation to improve their effectiveness. Semisynthetic substrates and sugar mimetics will be used as targets for enzymatic glycosylation. New synthetic glycosidase donors (azides, fluorides) will be developed and optimized. Regioselectivity of enzymatic glycosylations will be increased using partly protected sugars by chemoenzymatic acylation. Advanced NMR methodology and molecular modelling will be used for mechanistic studies of interactions of inhibitors and modified substrates with glycosidases and target proteins (receptors). As target structures ligands for the NKR-P1 receptor (NK cells) based on the aminosugars and derivatives of isoglobotriose (a-Gal structures) for xenotransplantation problems will be prepared by chemoenzymatic procedures and the compounds will be tested in biological systems (in vitro and ex vivo).
Overall production of the WG is documented in 47 full papers in int. journals, from that 34 papers involves two or more groups, which clearly demonstrates broad networking.
COST provided mobility resources that were crucial virtually in all works (see papers) where 2 groups participated. Description of each topic even by few lines would make he report extremely long, therefore we have chosen only the most importatant achievements as above.
All planned tasks were fulfilled – the project was carefully prepared and it was based on various preceeding bilateral cooperation, therefore all the tasks were based on the previous successfull pilot experiments.
Kick-off meeting: October 12-13, 2002, Prague, Institute of Microbiology
|13.00 – 13.30||Welcome address, approval of agenda (Vladimir Kren)|
|Presentations of the groups|
|13.30 – 14.00||Chemoenzymatic Approaches to Carbohydrate Synthesis (Wolf-Dieter Fessner, D)|
|14.00 – 14.30||Selective Enzymatic Acylations of Carbohydrates and Their Application in Glycosidase-Catalysed|
|Synthesis (Daniela Monti, I) (head of group S. Riva)|
|14.30 – 15.00||Glycomimetics: C-Disaccharides, Imino-C-disaccharides and Analogs (Pierre Vogel, CH)|
|15.00 – 15.30||Bioactive Oligosaccharides (Christopher Bucke, GB)|
|15.30 – 16.00||alpha-Galactosidases in Synthesis of New Carbohydrate Structures (Mária Vršanská , SK)|
|16.00 – 16.30||Glycosidases in organic media – applications and perspectives (Patrick Adlercreutz, S)|
|16.30 – 17.00||Library of fungal glycosidases – its application and potential for the use within WG (Vladimir Kren, CZ)|
|17.00 – 17.30||Cofee Break|
|New groups accession (their presentation, discussion, voting) (V. Kren)|
|17.30 – 17.40||The use of native and immobilized a- and b-glucosidases and environmentally friendly solvents in reverse hydrolytic synthesis of a new group of detergent O-alkyl-glucosides (L. Boross, H)|
|17.40 – 17.50||beta-Glycosidase Catalyzed Upgrading of Lactose (Berndt Nidetzky, D)|
|17.50 – 18.00||Selectivity in Enzyme Inhibition: Synthesis of New Pyrrolidine Derivatives (Inmaculada Robina, E)|
|18.00 – 18.10||Discussion, voting (V. Kren)|
|18.10 – 18.30||Approval of working plans, STSMs, next workshop (V. Kren)|
|20.00 – 22.00||Working dinner|
Meeting participants photo