Lewis fucosyltransferase

R. Wischnat, R. Martin, C.-H. Wong, Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor , J. Org. Chem 1997, 63, 8361-8365. 

Galactoside 3(4)-L-fucosyltransferase [EC 2.4.1.65], also known as blood group Lewis a-4-fucosyltransferase, catalyzes the reaction of GDP-L-fucose with l,3-/3-D-galac-tosyl-A -acetyl-D-glucosaminyl-R to produce GDP and... 

Several fucosyltransferases have been isolated and used for in vitro synthesis. The Lewis A al,4-fucosyltransferase transfers unnatural fucose derivatives in from their GDP esters [23]. The enzyme al,3-fiicosyltransferase has been used to L-fucosylate the 3-position of the GlcNAc of A-acetyllactosamine and of sialyl a2,3-N-acetyllactosamine [24]. Several acceptor substrates with modifications in the GlcNAc residue could also be... 

Kukowsaka-Fatallo, J. F., R. D. Farsen, R. P. Nair, and J. B. Fowe, A cloned human cDNA determines expression of a mouse stage-specific embryonic antigen and the Lewis blood group a(l,3/l,4)fucosyltransferase. Genes Dev. 4 1288-1303, 1990. 

Enzymatic glycosylation on SP was first reported by Schuster et al. (157) and since then has been used to perform multiple glycosylations. Two examples are reported in Fig. 2.28. The synthesis of oligosaccharides 2.94 and 2.95 related to the sialyl Lewis X antigen was carried out via glycosylations mediated by P-l,4-galactosyltransferase and a-2,3-sialyltransferase (171) and by p-l,4-galactosyltransferase, a-2,3-sialyl-transferase, and fucosyltransferase (172), respectively. The use of unprotected saccha-... 

Table 2. Donorsubstrate specificity of Lewis a-(l 4)fucosyltransferase (Le-FucT)...

Auge C, Malleron A, Lubineau A, Tahrat H, Marc A, Goergen JL, Cerutti M, Steelant WFA, Delannoy P. Outstanding stability of immobilized recombinant (1 3/4)-fucosyltransferases exploited in the synthesis of Lewis A and Lewis X trisaccharides Chem. Commun. 2000 2017-2018. 

Rabina J, Smithers N, Britten CJ, Renkonen R. A time-resolved immunofluorometric method for the measurement of sialyl Lewis x-synthesizing alphal,3-fucosyltransferase activity. Anal. Biochem. 1997 246 71-78. 

An associated enzyme, al-3-fucosyltransferase, has also been used in syntheses to provide the Lewis x and sialyl Lewis x structural motifs [65]. Increasing availability of fucosyltransferases via cloning techniques are expected to have a strong influence on oligosaccharide synthesis in the near future. 

Here again, it is as probes that carba-oligosaccharides find their best applications. Compounds 7 and 8 were both submitted to the action of a-(l-3/4)-fucosyltransferase in the presence of GDP-fucose. Only 7 was accepted and fucosylated to give the Lewis analog 9 showing that this enzyme has a different mode of action regarding the synthesis of Lewis s (Scheme 8.3) [16]. 

U. B. Gokhale, O. Hindsgaul, and M. M. Palcic, Chemical synthesis of GDP-fucose analogs and their utilization by the Lewis a-l,4-fucosyltransferase. Can. J. Chem. 65 1063 (1990). 

Using an enzyme isolated from human milk,key polar groups on the acceptor and donor substrates have been decoded [48,92]. The availability of larger quantities of the recombinant form of fucosyltransferase III (Lewis-enzyme, EMBL accession no. X 53578) [93] allowed evaluation of the enzyme for preparative use with non-natural substrates [56,89,94,95]. 

Leucocyte adhesion deficiency type II (lADII) patients lack products of fucosyltransferases and therefore, they express the rare Bombay blood group phenotype and are negative for the Lewis blood group. They show severe mental retardation, are short in stature, and have dysmorphic features (low hairline, hypertelorism, broad... 

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