Arabinoamidine synthesis and its inhibition toward beta-glucosidase (sweet almonds) in comparison to a library of galactonoamidines
by Pickens, Jessica B.; Striegler, Susanne; Fan, Qiu-Hua
Aiming at the development of potent inhibitors of beta-glucosidases, a small library of galactonoamidines and one arabinoamidine derived in analogy were studied as inhibitors of sweet almond beta-glucosidase. The five-membered glycon in arabinoamidine was shown to interact with the proton donor in the active site of the retaining enzyme, but not with the nucleophile. By contrast, the corresponding galactonoamidine with a six-membered glycon and identical aglycon interacts with both hydrolysis-promoting amino acids in the active site and inhibits the enzymatic hydrolysis of beta-glucosides in the low nanomolar concentration range. While both inhibitors are competitive, their inhibition ability is more than 37,000-fold different.
- Journal
- Bioorganic and Medicinal Chemistry
- Volume
- 24
- Issue
- 16
- Year
- 2016
- Start Page
- 3371-3377
- URL
- https://dx.doi.org/10.1016/j.bmc.2016.04.069
- ISBN/ISSN
- 1464-3391; 0968-0896
- DOI
- 10.1016/j.bmc.2016.04.069