A-D-Fucosidases

Measurements of the activities of glycoside hydrolases in Bacillus species have shown that the relative activity of a-L-fucosidase differs from one species to another. The a-D-galactosidases in six strains of Streptomyces also displayed a-D-fucosidase activity, even after extensive purification, indicating that a single species is responsible for both activities. ... 

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>. 

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. 

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. 

An amidrazone (58) derived from 5-amino-5-deoxy-L-fuconolactam was found to inhibit a recombinant human a-L-fucosidase with a K -value of 820 nmol/1 [ 111 ]. A simple synthesis of 1,5-dideoxy-1,5-imino-D-arabinitol (59), previously prepared by Ganem et al. [49] as a potential maimosidase inhibitor, was applied to the affinity purification of a-L-fucosidase from bovine kidney by an improved method and the characterization of the enzyme thus obtained [112]. The relatively low affinity of this compound to the enzyme (Kj 2.2 pmol/1 at pH 7) compared to 1-deoxyfuconoJirimycin (51) turned out to be advantageous in terms of enzyme recovery and yield. Structurally related, suitably protected 5-amino-5-deoxy-D-arabinopyranose (60), was coupled with a N-acetyl-6-deoxy-6-thio-D-glucosaminide (61) to give a stable thioglycoside (62) [113]. 

A L-/wco-related analogue (71) of isofagomine [61], which was recently prepared from D-ribose by Ichikawa et al. following previously established chemistry [63,121], was found to be an a-L-fucosidase inhibitor with Kj 8 pmol/1. No inhibition was found with tetrazole derivatives such as (72) [ 122] obtained from L-gulonolactone. 

Fucosidase inhibiting l,4,5-trideoxy-l,4-imino-L-lyxitol (78) was prepared [124] from D-ribose via protected 5-amino-5-deoxy-L-lyxose (79) by a chemical route. This compound, as well as the 1-aminomethyl homologue (80), obtained by Kiliani-Fischer chain extension of (79), inhibited a-L-fucosidase with K around 2 pmol/1. l,4-Dideoxy-l,4-imino-D-iditol (81) [71] was found to be a moderate inhibitor of the enzyme. 

Fig. 3. —Proposed Structure of a Portion of theHemieellulosicXyloglucan of the Primary Cell-Wall of Dicots (After Albersheim5-64). [Heptasac-charide A and nonasaccharide B are derived from oligosaccharide C by the action of endo-(l—>4)-/ -D-glucanase at the bonds indicated by arrows. Pentasaccharide D is derived from "B by the combined action of a-L-fucosidase, a-D-xylosidase, and /J-D-glucosidase. A = L-arabinopyranose F = L-fucose G = D-glucose Gal = D-galactose X = D-xylose.]...

The xyloglucan from cell walls of Phaseolus coccineus39 contained l-arabinose, L-fucose, D-galactose, D-xylose, and D-glucose in the ratios of 4 6 9 34 46. Treatment with a-L-fucosidase released 85% of the l-fucose, and this fact, together with the results of methylation analysis, showed that L-fucose was present solely as terminal, a-linked groups. 

When bovine-comeal, peptido-keratan sulfate was degraded chemically, a tetrasaccharide fraction was obtained, and the sequence in this was determined from the hydrolytic pattern with E. coli jS-D-galactosidase, Canavalia ensiformis a-D-mannosidase (EC 3.2.1.24), human-placental / -D-mannosidase, and bovine-kidney a-L-fucosidase. 72... 

Chem. Soc. Chem. Commun. 1983, 835-836. Witczak, Z. J. Boryczewski, D. Thiosugars IV design and synthesis of S-linked fiicoside analogs as a new class of a-L-fucosidase inhibitors. Bioorg. Med. Chem. Lett. 1998, 8, 3265-3268. Kim, K. S. Hurh, E. Y. Youn, J. N. Park, J. I. Dialkyl (l-hydroxyiminoalkyl)phosphonates from 1-bromo-l-nitroalkanes and trialkyl phosphites./. Org. Chem. 1999, 64, 9272-9274. 

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