Inhibition of microbial β-N-acetylhexosaminidases by 4-deoxy- and galacto-analogues of NAG-thiazoline

[Display omitted] NAG-thiazoline is a well-established competitive inhibitor of two physiologically relevant glycosidase families—β-N-acetylhexosaminidases (GH20) and β-N-acetylglucosaminidases (GH84). Based on the different substrate flexibilities of these enzyme groups, we designed and synthesized the 4-deoxy derivative of NAG-thiazoline aiming at the selective inhibition of GH20 β-N-acetylhexosaminidases. One GH84 and two GH20 microbial glycosidases were employed as model enzymes for the inhibition assays. Surprisingly, the new compound 4-deoxy-thiazoline exhibited no activity inhibition with either of the enzyme families of interest. Unlike with the substrates, the 4-hydroxyl group of the inhibitor’s sugar ring seems to be crucial for binding the inhibitor to the active sites of these enzymes.