Jessica B Pickens1, Susanne Striegler2, Qiu-Hua Fan1. 1. University of Arkansas, Department of Chemistry and Biochemistry, 345 N Campus Drive, Fayetteville, AR 72701, USA. 2. University of Arkansas, Department of Chemistry and Biochemistry, 345 N Campus Drive, Fayetteville, AR 72701, USA. Electronic address: Susanne.Striegler@uark.edu.
Abstract
Aiming at the development of potent inhibitors of β-glucosidases, a small library of galactonoamidines and one arabinoamidine derived in analogy were studied as inhibitors of sweet almond β-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 β-glucosides in the low nanomolar concentration range. While both inhibitors are competitive, their inhibition ability is more than 37,000-fold different.
Aiming at the development of potent inhibitors of β-glucosidases, a small library of n class="Chemical">galactonoamidines and one arabinoamidine derived in analogy were studied as inhibitors of sweet almond β-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 β-glucosides in the low nanomolar concentration range. While both inhibitors are competitive, their inhibition ability is more than 37,000-fold different.
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