Fucosyltransferase inhibitor

Bryan MC, Lee LV, Wong CH. High-throughput identification of fucosyltransferase inhibitors using carbohydrate microarrays. Bioorg. Med. Chem. Lett. 2004 14 3185-3188. 

Recently, however, several such assays have been developed for the study of carbohydrate-enzyme interactions. As mentioned previously, carbohydrate microarrays can be employed for inhibitor identification. Indeed, they were recently used by Wong and coworkers to identify fucosyltransferase inhibitors from a small library (85 compounds) of triazole-containing compounds [46,... 

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. 

Fucosyltransferases (glycosyltransferases) promote the transfer of fucose from GDP-fucose onto a saccharidic acceptor. This transfer occurs with inversion of the configuration of the anomeric carbon. The inhibition has been studied with fluorinated substrates. GDP-2-fluoro-2-deoxyfucoses (GDP-2F-fucose) and GDP-6-fluoro-6-deoxyfucoses (GDP-6F-fucose) are competitive inhibitors. The values are close to or less than that of (Figure 1.29)P The very close values of GDP-2F-fucose... 

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. 

A heptaprenylhydroquinone derivative (402) was isolated from an Indian sample of Ircinia fasciculata [341]. Ircinia spinulosa from the Adriatic contained three sulfated 2-prenylhydroquinones (403-405) that are toxic to brine shrimp [342]. An Ircinia sp. from New Caledonia contained a sulfated 2-prenylhydroquinone (406) and a sulfated furanoterpene (407) [343]. An Australian Sarcotragus sp. contained octaprenylhydroquinone sulfate (408) and nonaprenylhydroquinone sulfate (409) as inhibitors of al,3 fucosyltransferase VH [344]. 

Palcic MM, Heerze LD, Srivastava OP, Hindsgaul O. A bisubstrate analog inhibitor for a (l- 2.-fucosyltransferase. J. Biol. Chem. 1989 264 17174-17181. 

Cai, S, Stroud, M R, Hakomori, S, Toyokuni, T, Synthesis of carbocyclic analogs of guanosine 5 -(beta-L-fucopyranosyl diphosphate) (GDP-fucose) as potential inhibitors of fucosyltransferases, J. Org. Chem., 57, 6693-6696, 1992. 

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. 

Variations of the radical acceptor substitution pattern and use of acetobromogalactose 242 [106] or acetobromomannose 243 [107,108] as a radical precursor has resulted in the s)uithesis of various C-dimers including the C-linked analog of Man-o (l— 3)-GalNAc, which proved to be an inhibitor of several glycosidases, as well as human a-kS-fucosyltransferase VI [108] (O Scheme 49). 

Lee LV, MitcheU ML, Huang S-J, Eokin W, Sharpless KB, Wong C-H (2003) A potent and highly selective inhibitor of human a-1, 3-fucosyltransferase via click chemistry. J Am Chem Soc 125 9588-9589... 

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