Disrupting N-Glycosylation Using Type I Mannosidase Inhibitors Alters B-Cell Receptor Signaling.

ABSTRACT: Kifunensine is a known inhibitor of type I α-mannosidase enzymes and has been shown to have therapeutic potential for a variety of diseases and application in the expression of high-mannose N-glycan bearing glycoproteins; however, the compound's hydrophilic nature limits its efficacy. We previously synthesized two hydrophobic acylated derivatives of kifunensine, namely, JDW-II-004 and JDW-II-010, and found that these compounds were over 75-fold more potent than kifunensine. Here we explored the effects of these compounds on different mice and human B cells, and we demonstrate that they affected the cells in a similar fashion to kifunensine, further demonstrating their functional equivalence to kifunensine in assays utilizing primary cells. Specifically, a dose-dependent increase in the for

SUBMITTER: Huang A 

PROVIDER: S-EPMC9667535 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature