Inhibition of glycosidases by aldonolactones of corresponding configuration. 2. Inhibitors of β-N-acetylglucosaminidase

Abstract

2-Acetamido-2-deoxygluconolactone (N-acetylglucosaminonolactone) was synthesized; this compound and 2-acetamido-2-deoxygalactonolactone (N-acetylgalactosaminonolactone) were very powerful competitive inhibitors of [beta]-N-acetylglucosaminidase from rat epididymis. These lactones also inhibited the [beta]-N-acetylglucosaminidase in the limpet, but less powerfully, and only N-acetylglucosaminonolactone, and then only at high concentration, had any effect upon [alpha]-N-acetylglucosaminidase. The free acids obtained by alkali treatment of the lactones were not inhibitors of [beta]-N-acetylglucosaminidase, but some reconversion into the lactones occurred at the acid pH of the enzyme assay. N-acetylgalactosaminonolactone was more stable than N-acetylglucosaminonolactone in pure aqueous solution or in buffers at physiological pH. The lactones and the acids derived from them underwent conversion in aqueous solution into equilibrium mixtures containing more than one species, the composition depending on the pH. In particular, there was some conversion of the known N-acetylgalactosaminonolactone into a more powerful but less stable inhibitor, probably the 1,5-lactone.