1350467-75-2

Upstream product

• 3082-96-0 methyl 1,2,3,4-tetra-O-acetyl-α,β-D-glucopyranosyluronate 
• 52173-67-8 methyl (2,4,6-trichlorophenyl 2,3,4-tri-O-acetyl-β-D-glucopyranosid)uronate 
• 21085-72-3 1-bromo-2,3,4-tri-O-acetyl-α-D-glucuronic acid methyl ester 
• 57820-69-6 (3R,4S,5S,6S)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 

Downstream Products

• 1350467-77-4 methyl (2,4,6-trichlorophenyl 2,3-di-O-acetyl-4-deoxy-5-C-bromo-4-{²H}-β-D-glucopyranosid)uronate 
• 1350467-78-5 methyl (2,4,6-trichlorophenyl 2,3-di-O-acetyl-4-deoxy-4-{(2)H}-α-L-threo-hex-4-enopyranosid)uronate 
• 1350467-69-4 2,4,6-trichlorophenyl 4-deoxy-α-L-threo-hex-4-enopyranosiduronic acid 
• 1350467-70-7 2,4,6-trichlorophenyl 4-deoxy-4-{(2)H}-α-L-threo-hex-4-enopyranosiduronic acid 

Relevant academic research and scientific papers

Mechanistic insights from substrate preference in unsaturated glucuronyl hydrolase

Natural and synthetic unsaturated glucuronides were tested as substrates for Clostridium perfringens unsaturated glucuronyl hydrolase to probe its mechanism and to guide inhibitor design. Of the natural substrates, a chondroitin disaccharide substrate with sulfation of the primary alcohol on carbon 6 of its N-acetylgalactosamine moiety was found to have the highest turnover number of any substrate reported for an unsaturated glucuronyl hydrolase, with kcat=112 s-1. Synthetic aryl glycoside substrates with electron-withdrawing aglycone substituents were cleaved more slowly than those with electron-donating substituents. Similarly, an unsaturated glucuronyl fluoride was found to be a particularly poor substrate, with k cat/Km=44 nM-1 s-1 - a very unusual result for a glycoside-cleaving enzyme. These results are consistent with a transition state with positive charge at carbon 5 and the endocyclic oxygen, as anticipated in the hydration mechanism proposed. However, several analogues designed to take advantage of strong enzyme binding to such a transition state showed little to no inhibition. This result suggests that further work is required to understand the true nature of the transition state stabilised by this enzyme. Copyright

Glycoside cleavage by a new mechanism in unsaturated glucuronyl hydrolases

Unsaturated glucuronyl hydrolases (UGLs) from GH family 88 of the CAZy classification system cleave a terminal unsaturated sugar from the oligosaccharide products released by extracellular bacterial polysaccharide lyases. This pathway, which is involved in extracellular bacterial infection, has no equivalent in mammals. A novel mechanism for UGL has previously been proposed in which the enzyme catalyzes hydration of a vinyl ether group in the substrate, with subsequent rearrangements resulting in glycosidic bond cleavage. However, clear evidence for this mechanism has been lacking. In this study, analysis of the products of UGL-catalyzed reactions in water, deuterium oxide, and dilute methanol in water, in conjunction with the demonstration that UGL rapidly cleaves thioglycosides and glycosides of inverted anomeric configuration (substrates that are resistant to hydrolysis by classical glycosidases), provides strong support for this new mechanism. A hydration-initiated process is further supported by the observed UGL-catalyzed hydration of a C-glycoside substrate analogue. Finally, the observation of a small β-secondary kinetic isotope effect suggests a transition state with oxocarbenium ion character, in which the hydrogen at carbon 4 adopts an axial geometry. Taken together, these observations validate the novel vinyl ether hydration mechanism and are inconsistent with either inverting or retaining direct hydrolase mechanisms at carbon 1.