SLC35D3 Inhibitors

Chemical inhibitors of SLC35D3 operate by disrupting the glycosylation process critical for the protein's proper folding and function. Benzyl-α-GalNAc can inhibit the addition of O-GlcNAc to serine and threonine residues on proteins, which is essential for their correct folding and function. This action can prevent SLC35D3 from achieving its functional conformation, thereby inhibiting its activity. Similarly, Swainsonine and Kifunensine target mannosidase II and mannosidase I, respectively. By inhibiting these enzymes, the glycosylation process necessary for SLC35D3 to reach its functional structure is disrupted, which can lead to the protein's transport activity being inhibited. Deoxymannojirimycin and 1-Deoxynojirimycin also inhibit mannosidase I, while Castanospermine and NB-DNJ inhibit glucosidase I and II. These enzymes are involved in trimming glucose residues, a step necessary for proper glycoprotein folding. Inhibition of these enzymes can result in an accumulation of misfolded glycoproteins, including SLC35D3, thereby impairing its function.

In addition, compounds like Celgosivir target glucosidase I, potentially preventing the proper folding of N-linked glycoproteins such as SLC35D3, resulting in its inhibited function. Brefeldin A disrupts the Golgi apparatus's function, leading to the mislocalization of proteins including SLC35D3, which can inhibit the protein's transport function. Tunicamycin inhibits the initial step in the synthesis of N-glycan precursors, which is crucial for N-linked glycosylation, and thus can inhibit the proper folding and function of SLC35D3. Monensin alters the pH and ion gradients within the Golgi apparatus, which may inhibit the correct trafficking and function of SLC35D3. These chemicals target the biosynthetic pathway of glycoproteins directly linked to the maturation and function of SLC35D3, thereby inhibiting its transport activity within the cell.