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

Publication date: Available online 7 May 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Jessica B. Pickens, Susanne Striegler, Qiu-Hua Fan
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.

Graphical abstract

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1TwXMR6
via IFTTT