Endoglycosidase H Activators

Endoglycosidase H activators are a series of chemical inhibitors that target various glycosidases involved in the maturation and processing of N-glycans, leading to an increase in the availability of high-mannose and hybrid-type oligosaccharides, which are the preferred substrates for Endoglycosidase H. The action of compounds such as Swainsonine, Castanospermine, Deoxymannojirimycin (DMJ), and Deoxynojirimycin (DNJ) on alpha-mannosidase and glucosidase disrupts the normal trimming of glucose and mannose residues from the N-glycan structures. This impediment causes an accumulation of glycoproteins that bear unprocessed glycans, thus indirectly promoting the enzymatic activity of Endoglycosidase H. Similarly, Kifunensine, 1-Deoxymannojirimycin, and Bromoconduritol target mannosidase I and glucosidases, enhancing the presence of the high-mannose N-glycans in the endoplasmic reticulum and Golgi apparatus, which are then cleaved by Endoglycosidase H, effectively increasing its functional output.

The functional enhancement of Endoglycosidase H is further supported by the action of Celgosivir, N-Butyldeoxynojirimycin, Miglustat, NN-DNJ, and Isofagomine, which serve as inhibitors for various enzymes that participate in the folding and maturation of glycoproteins. Celgosivir, by inhibiting alpha-glucosidase I, leads to the production of misfolded glycoproteins with high mannose structures that are not further processed and thus become available for Endoglycosidase H action. N-Butyldeoxynojirimycin and Miglustat, through their glucosidase inhibitory effects, create a similar outcome. NN-DNJ, a broad-spectrum iminosugar, and Isofagomine, a beta-glucosidase inhibitor, also contribute to the accumulation of Endoglycosidase H substrates. The coordinated action of these compounds results in an enhanced functional activity of Endoglycosidase H by maintaining a higher concentration of its specific substrates within the cellular milieu.