Title

Arabinoamidine synthesis and its inhibition toward β-glucosidase (sweet almonds) in comparison to a library of galactonoamidines

Document Type

Article

Publication Date

2016

Keywords

Amidine, Azasugar, Carbohydrate, Inhibition, β-Glucosidase

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.

Comments

Support of this research to S.S. by the National Science Foundation (CHE-1305543) and the Arkansas Biosciences Institute is gratefully acknowledged. The facilities used in this study were supported by Grant Number P30 GM103450 from the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH).

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