title: Design and synthesis of substrate and internal standard conjugates for profiling enzyme activity in the Sanfilippo syndrome by affinity chromatography/electrospray ionization mass spectrometry.
abstract: We describe the design and synthesis of substrate and internal standard conjugates for application in profiling enzyme activity of the enzymes alpha-D-2-deoxy-2-N-sulfonamido-glucosamine sulfamidase, alpha-D-2-deoxy-2-N-acetyl-glucosamine hydrolase, acetyl-coenzymeA:alpha-D-2-deoxy-2-amino-glucosamine transferase, and alpha-D-2-deoxy-2-N-acetyl-glucosamine-6-sulfate sulfatase. Deficiency of any one of these enzymes results in a single clinical phenotype known as Sanfilippo syndrome. Such substrates have been proven effective in the confirmation of enzyme deficiency by a combination of affinity chromatography (AC) and electrospray ionization mass spectrometry (ESIMS), which forms the foundation for a new analytical technology (ACESIMS) of general interest and application to clinical and biomedical research.
authors.affiliation: Departments of Chemistry and Biochemistry, Bagley Hall, Box 351700, University of Washington, Seattle, Washington 98195-1700, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Gerber
authors.forename: F
authors.initials: F
authors.lastname: Turecek
authors.forename: M H
authors.initials: MH
authors.lastname: Gelb
mesh_terms: D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D002846:Chromatography, Affinity; D004789:Enzyme Activation / Q000502:physiology; D005944:Glucosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D006801:Humans; D006867:Hydrolases / Q000032:analysis* / Q000172:deficiency; D009084:Mucopolysaccharidosis III / Q000175:diagnosis / Q000201:enzymology*; D009087:Mucopolysaccharidosis VI; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000032:analysis*; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization; D013379:Substrate Specificity
chemical_list: C046735:N-acetylgalactosamine 4-sulfate; D006867:Hydrolases; D020051:N-Acetylgalactosamine-4-Sulfatase; C022708:N-sulfoglucosamine sulfohydrolase; D000116:Acetylgalactosamine; D005944:Glucosamine