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Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides.
Miller, Rebecca L; Guimond, Scott E; Schwörer, Ralf; Zubkova, Olga V; Tyler, Peter C; Xu, Yongmei; Liu, Jian; Chopra, Pradeep; Boons, Geert-Jan; Grabarics, Márkó; Manz, Christian; Hofmann, Johanna; Karlsson, Niclas G; Turnbull, Jeremy E; Struwe, Weston B; Pagel, Kevin.
Affiliation
  • Miller RL; Copenhagen Center for Glycomics, Department of Cellular & Molecular Medicine, University of Copenhagen, Copenhagen, N 2200, Denmark. rmiller@sund.ku.dk.
  • Guimond SE; Centre for Glycobiology, Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK. rmiller@sund.ku.dk.
  • Schwörer R; Laboratory of Cancer Biology, Department of Oncology, Medical Sciences Division, University of Oxford, Old Road Campus Research Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7DQ, UK. rmiller@sund.ku.dk.
  • Zubkova OV; Centre for Glycobiology, Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool, L69 7ZB, UK.
  • Tyler PC; Institute for Science and Technology in Medicine, School of Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK.
  • Xu Y; Ferrier Research Institute, Victoria University of Wellington, 69 Gracefield Road, Gracefield, Lower Hutt, 5010, New Zealand.
  • Liu J; Ferrier Research Institute, Victoria University of Wellington, 69 Gracefield Road, Gracefield, Lower Hutt, 5010, New Zealand.
  • Chopra P; Ferrier Research Institute, Victoria University of Wellington, 69 Gracefield Road, Gracefield, Lower Hutt, 5010, New Zealand.
  • Boons GJ; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
  • Grabarics M; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 27599, USA.
  • Manz C; Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA, 30602, USA.
  • Hofmann J; Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA, 30602, USA.
  • Karlsson NG; Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Science, and Bijvoet Center for Biomolecular Research, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
  • Turnbull JE; Freie Universitaet Berlin, Institute of Chemistry and Biochemistry, Takustrasse 3, 14195, Berlin, Germany.
  • Struwe WB; Fritz Haber Institute of the Max Planck Society, Faradayweg 4-6, 14195, Berlin, Germany.
  • Pagel K; Freie Universitaet Berlin, Institute of Chemistry and Biochemistry, Takustrasse 3, 14195, Berlin, Germany.
Nat Commun ; 11(1): 1481, 2020 03 20.
Article in En | MEDLINE | ID: mdl-32198425
Despite evident regulatory roles of heparan sulfate (HS) saccharides in numerous biological processes, definitive information on the bioactive sequences of these polymers is lacking, with only a handful of natural structures sequenced to date. Here, we develop a "Shotgun" Ion Mobility Mass Spectrometry Sequencing (SIMMS2) method in which intact HS saccharides are dissociated in an ion mobility mass spectrometer and collision cross section values of fragments measured. Matching of data for intact and fragment ions against known values for 36 fully defined HS saccharide structures (from di- to decasaccharides) permits unambiguous sequence determination of validated standards and unknown natural saccharides, notably including variants with 3O-sulfate groups. SIMMS2 analysis of two fibroblast growth factor-inhibiting hexasaccharides identified from a HS oligosaccharide library screen demonstrates that the approach allows elucidation of structure-activity relationships. SIMMS2 thus overcomes the bottleneck for decoding the informational content of functional HS motifs which is crucial for their future biomedical exploitation.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oligosaccharides / Mass Spectrometry / Heparitin Sulfate / Ions Type of study: Prognostic_studies Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Document type: Article Affiliation country: Denmark Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oligosaccharides / Mass Spectrometry / Heparitin Sulfate / Ions Type of study: Prognostic_studies Language: En Journal: Nat Commun Journal subject: BIOLOGIA / CIENCIA Year: 2020 Document type: Article Affiliation country: Denmark Country of publication: United kingdom