title: Inhibition of the alpha-L-arabinofuranosidase III of Monilinia fructigena by 1,4-dideoxy-1,4-imino-L-threitol and 1,4-dideoxy-1,4-imino-L-arabinitol.
abstract: 1. 1,4-Dideoxy-1,4-imino-L-threitol was synthesized and the synthesis of 1,4-dideoxy-1,4-imino-L-arabinitol was improved. 2. Both compounds are competitive inhibitors of Monilinia fructigena alpha-L-arabinofuranosidase III, the additional hydroxymethyl group in the arabinitol contributing about 17.8 kj/mol (4.25 kcal/mol) to the Gibbs free energy of binding. 3. The affinities (1/Ki) of both compounds vary with pH in a classical bell-shaped way, the pKa value being that of the acid-catalytic group on the enzyme [5.9; Selwood & Sinnott (1988) Biochem. J. 254, 899-901] and the pKb values being those of the free inhibitors, 7.6 and 7.8 respectively. 4. On the basis of these and literature data we suggest that efficient inhibition of a glycosidase at its pH optimum by an appropriate iminoalditol will be found when the pKa of the iminoalditol is below that of the acid-catalytic group of the target enzyme.
authors.affiliation: Department of Organic Chemistry, University of Bristol, U.K.
authors.forename: M T
authors.initials: MT
authors.lastname: Axamawaty
authors.forename: G W
authors.initials: GW
authors.lastname: Fleet
authors.forename: K A
authors.initials: KA
authors.lastname: Hannah
authors.forename: S K
authors.initials: SK
authors.lastname: Namgoong
authors.forename: M L
authors.initials: ML
authors.lastname: Sinnott
mesh_terms: D001089:Arabinose; D001203:Ascomycota / Q000201:enzymology*; D001667:Binding, Competitive; D003837:Deoxy Sugars / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006863:Hydrogen-Ion Concentration; D050113:Imino Furanoses; D013402:Sugar Alcohols / Q000494:pharmacology*; D013780:Tetroses; D013816:Thermodynamics
chemical_list: D003837:Deoxy Sugars; D050113:Imino Furanoses; D013402:Sugar Alcohols; D013780:Tetroses; C058137:1,4-dideoxy-1,4-iminoarabinitol; C063290:1,4-dideoxy-1,4-iminothreitol; D001089:Arabinose; D006026:Glycoside Hydrolases; C019713:alpha-N-arabinofuranosidase