title: Glycosynthase-mediated synthesis of glycosphingolipids.
abstract: Glycosphingolipids play crucial roles in virtually every stage of the cell cycle, and their clinical administration has been proposed as a treatment for Alzheimer's, Parkinson's, stroke, and a range of other conditions. However, lack of supply has severely hindered testing of this potential. A novel glycosynthase-based synthetic strategy is demonstrated, involving a mutant of an endoglycoceramidase in which the catalytic nucleophile has been ablated. This mutant efficiently couples a range of glycosyl fluoride donors with a range of sphingosine-based acceptors in yields around 95%. This technology opens the door to large-scale production of glycosphingolipids and, thus, to clinical testing.
authors: Protein Engineering Network of Centres of Excellence, Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Mark D
authors: MD
authors: Vaughan
authors: Karl
authors: K
authors: Johnson
authors: Shawn
authors: S
authors: DeFrees
authors: Xiaoping
authors: X
authors: Tang
authors: R Antony J
authors: RA
authors: Warren
authors: Stephen G
authors: SG
authors: Withers