title: Glycosynthase mediated synthesis of psychosine.
abstract: Globoid cell leukodystrophy (GCL), or Krabbe disease, is a lysosomal storage disorder characterized by a deficiency in galactosylceramidase (GALC), which hydrolyses galactosylceramide and galactosylsphingosine (psychosine). Early detection of GCL in newborns is essential for timely therapeutic intervention and could be achieved by testing infant blood samples with isotopically labeled lysosmal enzyme substrates and mass spectrometry. While isotopically labeled psychosine would be a useful tool for the early diagnosis of GCL, its synthesis is lengthy and expensive. To obviate this problem we developed a one-step chemoenzymatic synthesis of psychosine using a glycosynthase mutant of the Rhodococcus equi endogalactosylceramidase (EGALC), α-D-galactopyranosyl fluoride and sphingosine.
authors.affiliation: Centre for High-Throughput Biology, Michael Smith Laboratories, 185 East Mall, Vancouver, British Columbia, V6T 1Z4, Canada; Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, V6T 1Z1 Canada.
authors.forename: Ethan D
authors.initials: ED
authors.lastname: Goddard-Borger
authors.affiliation: Centre for High-Throughput Biology, Michael Smith Laboratories, 185 East Mall, Vancouver, British Columbia, V6T 1Z4, Canada; Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, V6T 1Z1 Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Tysoe
authors.affiliation: Centre for High-Throughput Biology, Michael Smith Laboratories, 185 East Mall, Vancouver, British Columbia, V6T 1Z4, Canada; Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, V6T 1Z1 Canada. Electronic address: withers@chem.ubc.ca.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Withers
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D042241:Early Diagnosis; D005698:Galactosylceramidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007965:Leukodystrophy, Globoid Cell / Q000175:diagnosis; D009005:Monosaccharides / Q000737:chemistry*; D009154:Mutation; D011609:Psychosine / Q000096:biosynthesis*; D016929:Rhodococcus equi / Q000201:enzymology / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D009005:Monosaccharides; C457441:galactopyranosyl fluoride; D011609:Psychosine; D005698:Galactosylceramidase
keywords: Globoid cell leukodystrophy; Glycosynthase; Infant screening; Psychosine