Arabinoamidine synthesis and its inhibition toward β-glucosidase (sweet almonds) in comparison to a library of galactonoamidines.
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.
University of Arkansas, Department of Chemistry and Biochemistry, 345 N Campus Drive, Fayetteville, AR 72701, USA.
Jessica B
JB
Pickens
University of Arkansas, Department of Chemistry and Biochemistry, 345 N Campus Drive, Fayetteville, AR 72701, USA. Electronic address: Susanne.Striegler@uark.edu.
Susanne
S
Striegler
University of Arkansas, Department of Chemistry and Biochemistry, 345 N Campus Drive, Fayetteville, AR 72701, USA.
Qiu-Hua
QH
Fan
D000578:Amidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006868:Hydrolysis; D007700:Kinetics; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000578:Amidines; D004791:Enzyme Inhibitors; D001617:beta-Glucosidase
Amidine; Azasugar; Carbohydrate; Inhibition; β-Glucosidase