Biosynthesis Rescue

Synthetic glycolipids for the treatment of rare diseases GPI-Anchored Proteins Biosynthesis Rescue We established a synthetic strategy for the chemical synthesis of glycosylphosphatidylinositols having unsaturated lipids. This strategy was used in a project with the group of Prof. Taroh Kinoshita from Osaka University and the Max Planck Institute of Colloids and Interfaces to investigate the biosynthesis of GPI-anchored proteins (GPI-APs). We designed, synthesized, and used GPI fragments to rescue the biosynthesis of GPI-APs caused by a mutation in genes involved in assembling GPI-glycolipids in cells. We demonstrated that the synthetic fragments GlcNAc-PI, Man-GlcN-PI, and GlcN-PI with two and three lipid chains rescue the deletion of the GPI biosynthesis in cells devoid of the PIGA, PIGL, and PIGW genes in vitro. The compounds allowed for concentration-dependent recovery of GPI biosynthesis and were highly active on the cytoplasmic face of the endoplasmic reticulum membrane. These synthetic molecules lead to…