Cameron_et_al-2019-Journal_of_Labelled_Compounds_and_Radiopharmaceuticals.pdf (1000.73 kB)
Synthesis of 13 C-labelled sulfated N-acetyl-d-lactosamines to aid in the diagnosis of mucopolysaccharidosis diseases
journal contribution
posted on 2021-11-18, 19:38 authored by Scott CameronScott Cameron, Olga ZubkovaOlga Zubkova, S Toms, Richard FurneauxRichard Furneaux, Phillip RendlePhillip RendleMorquio A syndrome is an autosomal mucopolysaccharide storage disorder that leads to accumulation of keratan sulfate. Diagnosis of this disease can be aided by measuring the levels of keratan sulfate in the urine. This requires the liquid chromatography tandem mass spectrometry (LCMS/MS) measurement of sulfated N-acetyl-d-lactosamines in the urine after cleavage of the keratan sulfate with keratanase II. Quantification requires isotopically-labelled internal standards. The synthesis of these 13 C 6 -labelled standards from 13 C 6 -galactose and N-acetylglucosamine is described. The required protected disaccharide is prepared utilising a regioselective, high yielding β-galactosylation of a partially protected glucosamine acceptor and an inverse addition protocol. Subsequent synthesis of the 13 C 6 -labelled mono and disulfated N-acetyllactosamines was achieved in five and eight steps, respectively, from this intermediate to provide internal standards for the LCMS/MS quantification of keratan sulfate in urine.
History
Preferred citation
Cameron, S. A., Zubkova, O. V., Toms, S., Furneaux, R. H. & Rendle, P. M. (2019). Synthesis of 13 C-labelled sulfated N-acetyl-d-lactosamines to aid in the diagnosis of mucopolysaccharidosis diseases. Journal of Labelled Compounds and Radiopharmaceuticals, 62(2), 67-76. https://doi.org/10.1002/jlcr.3697Publisher DOI
Journal title
Journal of Labelled Compounds and RadiopharmaceuticalsVolume
62Issue
2Publication date
2019-02-01Pagination
67-76Publisher
WileyPublication status
PublishedOnline publication date
2018-12-11ISSN
0362-4803eISSN
1099-1344Language
enUsage metrics
Categories
Keywords
C-13-labelledkeratan sulfatelactosamineMorquio AMPS IVAsulfated13C-labelledAcetylgalactosamineCarbon IsotopesKeratan SulfateMass SpectrometryMolecular Diagnostic TechniquesMucopolysaccharidosis IVRare DiseasesScience & TechnologyLife Sciences & BiomedicinePhysical SciencesBiochemical Research MethodsChemistry, MedicinalChemistry, AnalyticalBiochemistry & Molecular BiologyPharmacology & PharmacyChemistryKERATAN SULFATEPRACTICAL SYNTHESISLC-MS/MSMORQUIOACETYLLACTOSAMINEIVADISACCHARIDESANALOGSENZYMEMedicinal & Biomolecular ChemistryAnalytical Chemistry not elsewhere classifiedPharmacology and Pharmaceutical Sciences not elsewhere classifiedOrganic Chemistry