Fucosidases

The guanidino analogue 90 of the 7-membered cyclic urea system was prepared, enantiomerically pure, from D-mannitol. The derivative 90 selectively inhibits bovine kidney a-L-fucosidase at 2.8pM <00BMC307>. 

Figure 14. a) The putative transition states for the fucosidase- and fucosyltransferase-catalyzed reactions, b) Iminocyclitol transition state analogs which may be used... 

Instead of a triflate, the electrophile on the glycosyl acceptor can be an a,(3-unsaturated carbonyl group. This is the case reported in Fig. 25, in which a stereoselective Michael addition of the 1-thiosugar 56 to the a,(3-conjugated system of levoglucosenone 57, generated after deprotection a couple of L-fucopyranosyl-4-thiodisaccharides 61 and 62 presenting inhibitory activity on a-L-fucosidase.54... 

Besides (thio)glycosynthases and thioglycoligases, several other mutant glycosidases were produced with abolished hydrolytic activity in favour of synthesis transsialidase from Trypanosoma rangeli37 or p-transglycosidase from Thermits thermophilus.153 A new p-fucosidase activity was introduced into E. coli p-galactosidase by genetic manipulation.37... 

Exoglycosidases that are useful in carbohydrate degradations include neuraminidases, fucosidases, galactosidases, mannosidases, and aminohexosidases.76,77 An example of the use of degradation by a gly-cosidase in conjunction with methylation analysis is a study on the oc-... 

Scheme 6.3 Syntheses of Shimofuridin analog and fucosidase substrate.

Parikh, M.R. and Matyoumara, I., Site-saturation mutagenesis is more efficient than DNA shuffling for the directed evolution of / -fucosidase. J. Mol Biol, 2005, 352, 621-628. 

This enzyme [EC 3.2.1.55], also called arabinosidase, catalyzes the hydrolysis of terminal nonreducing a-L-arabinofuranoside residues in a-L-arabinosides. Actual substrates include a-L-arabinofuranosides, a-L-arabi-nans containing (1,3)- and/or (l,5)-linkages, arabinoxy-lans, and arabinogalactans. It should be noted that some /3-galactosidases and )3-D-fucosidases will also hydrolyze a-L-arabinosides. 

Selected from among their contributions were the first example of a synthetic furanoid iminoalditol, l,4-dideoxy-l,4-imino-D-mannitol (19, Scheme 7) 49 the first synthesis of the powerful L-fucosidase inhibitor l,5-dideoxy-l,5-imino-L-fucitol (20),50 the synthesis and structure confirmation of l,4-dideoxy-l,4-imino-D-arabinitol... 

The inverting GH 95 1,2-oc-L-fucosidase (EC 3.2.1.63) from Bifidobacterium bifi-dum in complex (PDB 2EAC) with 1-deoxy-L-fuconojirimycin (20) showed the inhibitor in C4 chair conformation, resembling L-fucose and the entrance to the active site was narrowed by the gate keeper loops.315 A calcium ion associated with the protein was not involved in the catalytic process but was considered to stabilize the enzyme. 

A. Lammerts van Bueren, A. Ardevol, J. Fayers-Kerr, B. Luo, Y. Zhang, M. Sollogoub, Y. Bleriot, C. Rovira, and G. J. Davies, Analysis of the reaction coordinate of a-L-fucosidases A combined structural and quantum mechanical approach,./. Am. Chem. Soc., 132 (2010) 1804-1806. 

M. Nagae, A. Tsuchiya, T. Katayama, K. Yamamoto, S. Wakatsuki, and R. Kato, Structural basis of the catalytic reaction mechanism of novel 1,2-a-L-fucosidase from Bifidobacterium bifidum, J. Biol. Chem., 282 (2007) 18497-18509. 

A. Ak, S. Prudent, D. LeNouen, A. Defoin, and C. Tamus, Synthesis of all-cis 2,5-imino-2,5-dideoxy-fucitol and its evaluation as a potent fucosidase and galactosidase inhibitor, Bioorg. Med. Chem. Lett., 20 (2010) 7410-7413. 

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