Inhibitors of β-Glucosidases of Animal Tissues

Abstract

Our first effort in the field of glucocerebroside manip­ulation stemmed directly from an observation by one of this meeting’s sponsors, Dr. Shimon Gatt. Dr. Gatt had purified glucocerebrosidase from brain to a certain degree and, in studying its properties, found that sphingosine produced good inhibition (1). It seemed likely that we could increase the strength and specificity of the effect by adding a glucosyl moiety to the sphingosine. John Erickson and I prepared glu­cosyl sphingosine from Gaucher spleen cerebroside and found that it was indeed a stronger inhibitor (2). When the com­pounds were tested with rat spleen cerebrosidase at the 0.3 mM level, sphingosine produced 59% inhibition and the glucoside produced 75% inhibition. Galactosyl sphingosine, the β-galac­toside made from brain cerebroside, had no effect at all, showing that the sugar residue was very important.