Expeditious Synthesis of a Trisubstrate Analogue for α(1→3)Fucosyltransferase

Heskamp, B. M.; Marel, Gijsbert A. van der; Boom, J. H. Van

doi:10.1080/07328309508005410

Cited by 11 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, these approaches only produced inhibitors with either comparable or slightly increased activity compared to that of the product inhibitor GDP. Very recently, trisubstrate analogs of α-1,3-fucosyltransferase containing d -glucose or N -acetyl- d -glucosamine, l -fucose analogs, and GDP have been synthesized as potential inhibitors, but no inhibition analysis was reported …”

Section: Introductionmentioning

confidence: 99%

Synergistic Inhibition of Human α-1,3-Fucosyltransferase V

et al. 1996

View full text Add to dashboard Cite

Human R-1,3-fucosyltransferase V (FucT V), which catalyzes the transfer of L-fucose moiety from guanosine diphosphate -L-fucose (GDP-Fuc) to an acceptor sugar to form sialyl Lewis x (sLe x ), was shown to proceed through an ordered, sequential mechanism by product inhibition studies. The designed azatrisaccharide propyl 2-acetamido- (2), prepared by covalently linking the N-group of -L-homofuconojirimycin (1) to the 3-OH of LacNAc through an ethylene unit, in the presence of GDP was found to be an effective inhibitor of FucT V. In the presence of 30 µM GDP, the concentration of 2 necessary to cause 50% inhibition was reduced 77-fold to 31 µM. Presumably, the azatrisaccharide and GDP form a complex which mimics the transition state of the enzymatic reaction. Given the low affinity of FucT V for its substrate LacNAc (K m ) 35 mM), the designed azatrisaccharide in the presence of GDP represents the most potent synergistic inhibitor complex reported so far.

show abstract

Section: Introductionmentioning

confidence: 99%

Synergistic Inhibition of Human α-1,3-Fucosyltransferase V

et al. 1996

View full text Add to dashboard Cite

show abstract

“…10% (Scheme 6 Tables 1 and 2. Having our three target disaccharides 20, 22 and 24, the last steps were aimed at the removal of the NAP ethers and the regeneration of the OH-2 0 , OH-3 0 and OH-4 0 . It was shown earlier that the NAP ethers could be hydrogenolyzed in the presence of benzyl ethers and esters 28 and they are less sensitive to acids than the p-methoxybenzyl ethers. The most important observation, however, is that the NAP ethers can easily be removed by DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) under conditions when the other usual protecting groups such as acetyl, pivaloyl, phthalimido, benzyl and benzylidene survive.…”

Section: Synthesis Of Partially Protectedmentioning

confidence: 99%

Synthesis of fully protected α-l-fucopyranosyl-(1→2)-β-d-galactopyranosides with a single free hydroxy group at position 2′, 3′ or 4′ using O-(2-naphthyl)methyl (NAP) ether as a temporary protecting group

Szabó¹,

Borbás²,

Bajza³

et al. 2005

Tetrahedron: Asymmetry

View full text Add to dashboard Cite

“…Nevertheless, very good inhibition activities (K i = 2.3 lM in competition with phenyl b-D-galactoside; K i = 16 lM in competition with GDP-fucose) were ob- Several examples of bisubstrate-analogous inhibitors of a(1-3)fucosyltransferase, which transfers fucose to the 3-OH group of N-acetylglucosamine (N-acetyllactosamine) moieties, have been reported (Scheme 23.40). Compound 145 contains the acceptor substrate and the donor substrate, one phosphate having been replaced by an ethylene group [204]. Unfortunately, inhibition data are not yet available.…”

Section: Bisubstrate Analogues As Inhibitorsmentioning

confidence: 99%