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.
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.
Axamawaty
M T
MT
Department of Organic Chemistry, University of Bristol, U.K.
Fleet
G W
GW
Hannah
K A
KA
Namgoong
S K
SK
Sinnott
M L
ML
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
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