Gaucher disease (GD), caused by a defect of beta-glucosidase (beta-Glu), is the most common form of sphingolipidosis. We have previously shown that a carbohydrate inimic N-octyl-beta-valienainine (NOV), an inhibitor of beta-Glu, could increase the protein level and enzyme activity of F2131 mutant beta-Glu in cultured GD fibroblasts, Suggesting that NOV acted asa pharmacological chaperone to accelerate transport and maturation of this mutant enzyme. In the current study, NOV effects were evaluated in GD fibroblasts with various beta-Glu mutations and in COS cells transiently expressing recombinant mutant proteins. In addition to F2131, NOV was effective on N 188S, G202R and N370S mutant forms of beta-Glu, whereas it was ineffective on G 193W, D409H and L444P mutants. When expressed in COS cells, the mutant proteins as well as the wild-type protein were localized predominantly in the endoplasmic reticulum and were sensitive to Endo-H treatment. NOV did not alter this localization or Endo-H sensitivity, suggesting that it acted in the endoplasmic reticulum. Profiling of N-alkyl-beta-valienamines with various lengths of the acyl chain showed that N-dodecyl-beta-valienamine was as effective as NOV. These results suggest a potential therapeutic value of NOV and related compounds for GD with a broad range of beta-Glu mutations. (C) 2007 Elsevier B.V. All rights reserved.