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dc.contributor.author Yasuda, Kayo
dc.contributor.author Fan, J. -. Q.
dc.contributor.author Kizu, Haruhisa
dc.contributor.author Molyneux, R. J.
dc.contributor.author Nash, Robert J.
dc.contributor.author Kato, Atsushi
dc.contributor.author Asano, Naoki
dc.contributor.author Fleet, George W. J.
dc.date.accessioned 2009-11-10T11:28:35Z
dc.date.available 2009-11-10T11:28:35Z
dc.date.issued 2001-01
dc.identifier.citation Yasuda , K , Fan , J Q , Kizu , H , Molyneux , R J , Nash , R J , Kato , A , Asano , N & Fleet , G W J 2001 , ' Novel alpha-L-fucosidase inhibitors from the bark of Angylocalyx pynaertii (Leguminosae) ' European Journal of Biochemistry , vol 268 , no. 35-41 , pp. 35-41 . , 10.1046/j.1432-1327.2001.01837.x en
dc.identifier.issn 1742-4658
dc.identifier.other PURE: 128189
dc.identifier.other dspace: 2160/3473
dc.identifier.uri http://hdl.handle.net/2160/3473
dc.description Asano, N., Yasuda, K., Kizu, H., Kato, A., Fan, J-Q., Nash, R. J., Fleet, G. W. J., Molyneux, R. J. (2001). Novel alpha-L-fucosidase inhibitors from the bark of Angylocalyx pynaertii (Leguminosae). European Journal of Biochemistry, 268, 35-41. Sponsorship: Special Research Fund of Hokuriku University (N. A.) en
dc.description.abstract The extract of bark of Angylocalyx pynaertii (Leguminosae) was found to potently inhibit mammalian α- l-fucosidases. A thorough examination of the extract resulted in the discovery of 15 polyhydroxylated alkaloids, including the known alkaloids from seeds of this plant, 1,4-dideoxy-1,4-imino- d-arabinitol (DAB), 1-deoxymannojirimycin (DMJ) and 2,5-imino-1,2,5-trideoxy- d-mannitol (6-deoxy-DMDP). Among them, eight sugar-mimic alkaloids showed the potent inhibitory activity towards bovine epididymis α- l-fucosidase and their Ki values are as follows: 6-deoxy-DMDP (83 µm), 2,5-imino-1,2,5-trideoxy- l-glucitol (0.49 µm), 2,5-dideoxy-2,5-imino- d-fucitol (17 µm), 2,5-imino-1,2,5-trideoxy- d-altritol (3.7 µm), DMJ (4.7 µm), N-methyl-DMJ (30 µm), 6-O-α- l-rhamnopyranosyl-DMJ (Rha-DMJ, 0.06 µm), and β- l-homofuconojirimycin (β-HFJ, 0.0053 µm). We definitively deduced the structural requirements of inhibitors of α- l-fucosidase for the piperidine alkaloids (DMJ derivatives). The minimum structural feature of α- l-fucosidase inhibitors is the correct configuration of the three hydroxyl groups on the piperidine ring corresponding to C2, C3 and C4 of l-fucose. Furthermore, the addition of a methyl group in the correct configuration to the ring carbon atom corresponding to C5 of l-fucose generates extremely powerful inhibition of α- l-fucosidase. The replacement of the methyl group of β-HFJ by a hydroxymethyl group reduced its inhibitory potential about 80-fold. This suggests that there may be a hydrophobic region in or around the active site. The existence or configuration of a substituent group on the ring carbon atom corresponding to the anomeric position of l-fucose does not appear to be important for the inhibition. Interestingly, Rha-DMJ was a 70-fold more potent inhibitor of α- l-fucosidase than DMJ. This implies that the lysosomal α- l-fucosidase may have subsites recognizing oligosaccharyl structures in natural substrates. en
dc.format.extent 7 en
dc.language.iso eng
dc.relation.ispartof European Journal of Biochemistry en
dc.title Novel alpha-L-fucosidase inhibitors from the bark of Angylocalyx pynaertii (Leguminosae) en
dc.type Text en
dc.type.publicationtype Article (Journal) en
dc.identifier.doi http://dx.doi.org/10.1046/j.1432-1327.2001.01837.x
dc.contributor.institution Aberystwyth University en
dc.contributor.institution Institute of Biological, Environmental and Rural Sciences en
dc.description.status Peer reviewed en


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