Probing the Inhibitor versus Chaperone Properties of sp²-Iminosugars towards Human β-Glucocerebrosidase: A Picomolar Chaperone for Gaucher Disease.

ABSTRACT: A series of sp²-iminosugar glycomimetics differing in the reducing or nonreducing character, the configurational pattern (d-gluco or l-ido), the architecture of the glycone skeleton, and the nature of the nonglycone substituent has been synthesized and assayed for their inhibition properties towards commercial glycosidases. On the basis of their affinity and selectivity towards GH1 β-glucosidases, reducing and nonreducing bicyclic derivatives having a hydroxylation profile of structural complementarity with d-glucose and incorporating an N′-octyl-isourea or -isothiourea segment were selected for further evaluation of their inhibitory/chaperoning potential against human glucocerebrosidase (GCase). The 1-deoxynojirimycin (DNJ)-related nonreducing conjugates behaved as st

SUBMITTER: Mena-Barragan T 

PROVIDER: S-EPMC6017062 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature