A-l,3-Fucosyltransferase

The iminoaltritol (74) as well as the iminogulitol (77) could also be shown to be moderate inhibitors of a recombinant human a-l,3-fucosyltransferase. 

In 2004, Strasser et al. generated a xylT knockout mutant that no longer produced [3(1,2)-linked xylosyltransferase, and nfucTA andfucTB double knockout mutant that was unable to produce a(l,3)-fucosyltransferase, in... 

A potent inhibitor against human a(l,3)-fucosyltransferase VI was identified from a GDP-triazole library of 85 compounds, which was produced by the Cu(I)-catalyzed [2 + 3] cycloaddition reaction between azide and acetylene, followed by in situ screening without product isolation (O Scheme 13) [155]. Kinetic evaluation of the purified inhibitor (O Scheme 13) showed that it is a competitive inhibitor against GDP-fucose with Ki = 62 nM, which would make this compound the first nanomolar and most potent inhibitor of Fuc-Ts. 

Since the chemical synthesis of oligosaccharides requires many synthetic steps including protection and deprotection procedures, the enzymatic approach has attracted much attention for the rapid s)uithesis of oligosaccharides. In addition, the perfect regio- and stereoselectivities of enzymatic methods with glycosyltransferases are quite attractive. Several transferases such as 8(l,4)-galactosyltransferase, a(l,3)-fucosyltransferase, and a-sialyltransferase have been used for polymer-supported enzymatic synthesis [70,71,72,73,74,75]. The selection of the pol)uner support is very important for the pol)uner-supported enz)unatic synthesis of oligosaccharides. 

Since sialic acid and fucose are important in the binding interaction of sialyl Lewisx to the selectins,45-50 a reasonable conjecture is that removal of fucose from sialyl Lewisx will completely stop the binding of leukocytes to the endothelium. Furthermore, this may be accomplished by inhibiting the activity of a-l,3-fucosyltransferase thus preventing the formation of sialyl Lewisx. 

Human a-l,3-fucosyltransferases are found in milk,51 53 saliva,54 and other specific cell lines.55-57 Through cloning studies, a role for an a-1,3-fucosyltransferase in cell adhesion was identified for the biosynthesis of sialyl Lewisxon neutrophils.58-59 As these studies link a-l,3-fucosyltransferase to cell adhesion and since the activated fucose species used by this enzyme is GDP-L-fucose, Luengo, et al.,eo prepared the C-glycoside analog of GDP-fucose shown in Figure 1.4.4. 

From Unsaturated Sizars. - A trisubstrate analogue 30 has been synthesized (Scheme 7) as a potential inhibitor of the a-(l- 3)-fucosyltransferase that transfers fucose from GDP-fucose onto 0-3 of a 2-acetamido-2-deoxy-P-D-glucose residue. The glycosyl donor 29 was synthesized from the L-fuconolactone derivative 28 by methylenation and anti-Markovnikov azido-phenylselenation,... 

Wakimoto, T, Maruyama, A, Matsunaga, S., Fusetani, N., Shinoda, K., and Murphy, P.T. (1999) Octa- and nonaprenylhydroquinone sulfates, inhibitors of a-l,3-fucosyltransferase Vll, from an Australian marine sponge Sarcotrugus sp. Biorg. Med. Chem. Lett., 9, 727-730. 

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