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: S A Gerber, F Turecek, M H Gelb
• Journal: Bioconjugate chemistry (Bioconjug Chem) 2001 Jul-Aug Vol. 12 Issue 4 Pg. 603-15 ISSN: 1043-1802 [Print] United States
• PMID: 11459466 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• N-acetylgalactosamine 4-sulfate
• Hydrolases
• N-Acetylgalactosamine-4-Sulfatase
• N-sulfoglucosamine sulfohydrolase
• Acetylgalactosamine
• Glucosamine

Topics

• Acetylgalactosamine (analogs & derivatives, chemical synthesis)
• Chromatography, Affinity
• Enzyme Activation (physiology)
• Glucosamine (analogs & derivatives, chemical synthesis)
• Humans
• Hydrolases (analysis, deficiency)
• Mucopolysaccharidosis III (diagnosis, enzymology)
• Mucopolysaccharidosis VI
• N-Acetylgalactosamine-4-Sulfatase (analysis)
• Reference Standards
• Spectrometry, Mass, Electrospray Ionization
• Substrate Specificity