Semin Thromb Hemost 2001; 27(5): 465-472
DOI: 10.1055/s-2001-17957
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

MALDI Mass Spectrometry as a Tool for Characterizing Glycosaminoglycan Oligosaccharides and their Interaction with Proteins

Luisa Sturiale, Annamaria Naggi, Giangiacomo Torri
  • Istituto di Chimica e Biochimica, G. Ronzoni Research Institute, Milan, Italy
Further Information

Publication History

Publication Date:
22 October 2001 (online)

ABSTRACT

Matrix-Assisted Laser Desorption Ionization (MALDI) mass spectrometry (MS) has emerged as a powerful, sensitive technique for structural analysis of glycosaminoglycans (GAGs) and their fractions and fragments. Whereas the molecular size of low sulfated or nonsulfated species (such as low-molecular weight [LMW] K5 polysaccharides) can be directly determined up to molecular weights (MWs) of 12 kD, polysulfated species require complexing with a basic polypeptide and at present can be characterized (in terms of both MW and end residues) up to the size of a decasaccharide, even in complex mixtures. MALDI spectra of GAG oligosaccharides in the presence of a complexing protein permit to assess binding to the protein and the presence of multimeric complexes.

REFERENCES

  • 1 Karas M, Bachmann D, Hillenkamp F. Influence of the wavelength in high-irradiance ultraviolet laser desorption mass spectrometry of organic molecules.  Anal Chem . 1985;  57 2935-2939
  • 2 Karas M, Bachmann D, Bahr U. Matrix-assisted ultraviolet laser desorption of non-volatile compounds.  Int J Mass Spectrom Ion Processes . 1987;  78 53-68
  • 3 Bahr U, Karas M, Hillenkamp F. Analysis of biopolymers by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry.  Fresenius J Anal Chem . 1994;  348 783-791
  • 4 Karas M, Hillenkamp F. Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons.  Anal Chem . 1988;  60 2299-2301
  • 5 Cohen S L, Chait B T. Influence of matrix solution conditions on the MALDI-MS analysis of peptides and proteins.  Anal Chem . 1996;  68 31-37
  • 6 Juhasz P, Roskey M T, Smirnov I P. Application of delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry to oligonucleotide analysis.  Anal Chem . 1996;  68 941-946
  • 7 Meri S, Letho T, Sutton C W. Structural composition and functional characterization of soluble CD59: heterogeneity of the oligosaccharide and glycophosphoinositol (GPI) anchor revealed by laser-desorption mass spectrometric analysis.  Biochem J . 1996;  316 923-935
  • 8 Wu K J, Odom R W. Characterizing synthetic polymers by MALDI MS.  Anal Chem . 1998;  70 456-461
  • 9 Harvey D J. Matrix-assisted laser desorption ionisation mass spectrometry of oligosaccharides and glycoconjugates.  J Chromatogr A . 1996;  720 429-446
  • 10 Karas M, Bahr U. Matrix-assisted laser desorption-ionization (MALDI) mass spectrometry: principles and applications. Selected topics, Mass Spectrom Biomolecular Sciences.  NATO ASI Series C . 1997;  504 33-53
  • 11 Juhasz P, Biemann K. Mass spectrometric molecular-weight determination of highly acidic compounds of biological significance via their complexes with basic polypeptides.  Proc Natl Acad Sci USA . 1994;  91 4333-4337
  • 12 Juhasz P, Biemann K. Utility of non-covalent complexes in the matrix-assisted laser desorption ionization mass spectrometry of heparin-derived oligosaccharides.  Carbohydr Res . 1995;  270 131-147
  • 13 Kjellen L, Lindahl U. Proteoglycans: structures and interactions.  Annu Rev Biochem . 1991;  60 443-475
  • 14 Casu B. Structure and biological activity of heparin.  Adv Carbohydr Chem Biochem . 1985;  43 51-134
  • 15 Lindahl U, Lidholt K, Spillmann D. More to ``heparin'' than anticoagulation.  Thromb Res . 1994;  75 1-32
  • 16 Harvey J H. Matrix-assisted laser desorption/ionization mass spectrometry of carbohydrates.  Mass Spectrom Rev . 1999;  18 349-451
  • 17 Keiser N, Venkataraman G, Shriver Z. Direct isolation and sequencing of specific protein-binding glycosaminoglycans.  Nat Med . 2001;  7 123-128
  • 18 Shriver Z, Raman R, Venkataraman G. Sequencing of 3-O-sulfate containing decasaccharides with a partial antithrombin III binding site.  Proc Natl Acad Sci USA . 2000;  97 10359-10364
  • 19 Yeung B, Marecak D. Molecular weight determination of hyaluronic acid by gel filtration chromatography coupled to matrix-assisted laser desorption ionization mass spectrometry.  J Chromatogr A . 1999;  852 573-581
  • 20 Schiller J, Arnhold J, Bernard S. Cartilage degradation by hyaluronate lyase and chondroitin ABC lyase: a MALDI-TOF mass spectrometric study.  Carbohydr Res . 1999;  318 116-122
  • 21 Vann W F, Schmidt M A, Jann B. The structure of the capsular polysaccharide (K5 antigen) of urinary-tract-infective Escherichia coli 010:K5:h4. A polymer similar to desulfo-heparin.  Eur J Biochem . 1981;  116 359-364
  • 22 Garozzo D, Impallomeni G, Spina E. Matrix-assisted laser desorption/ionization mass spectrometry of polysaccharides.  Rapid Commun Mass Spectrom . 1995;  9 937-941
  • 23 Casu B. Methods of structural analysis. In: Lane DA, Lindahl U, eds. Heparin: Chemistry and Biology London: Arnold 1989: 25-49
  • 24 Larnkjaer A, Hansen S H, Ostergaard P B. Isolation and characterization of hexasaccharides derived from heparin. Analysis by HPLC and elucidation of structure by 1H-NMR.  Carbohydr Res . 1995;  266 37-52
  • 25 Jeske W, Iqbal O, Gonella S. Pharmacologic profile of a low-molecular-weight heparin depolymerized by γ-irradiation.  Semin Thromb Hemost . 1995;  21 201-211
  • 26 Casu B, Oreste P, Torri G. The structure of heparin oligosaccharide fragments with high anti-(factor Xa) activity containing the minimal antithrombin III-binding sequence. Chemical and 13C-NMR studies.  Biochem J . 1997;  14(Suppl 1) S89(Abst)
  • 27 Faham S, Hileman R E, Fromm J R. Heparin structure and interactions with basic fibroblast growth factor.  Science . 1996;  271 1116-1120
  • 28 Hileman R E, Fromm J R, Weiler J M. Glycosaminoglycan-protein interactions: Definitions of consensus sites in glycosaminoglycan binding proteins.  Bioessays . 1998;  20 156-167
  • 29 Venkataraman G, Shriver Z, Davis J. Fibroblast growth factors 1 and 2 are distinct in oligomerization in the presence of heparin-like glycosaminoglycans.  Proc Natl Acad Sci USA . 1999;  96 1982-1987
  • 30 Venkataraman G, Shriver Z, Raman R. Sequencing complex polysaccharides.  Science . 1999;  286 537-542
  • 31 Venkataraman G, Sasisekharan V, Herr A B. Preferential self-association of basic fibroblast growth factor is stabilised by heparin during receptor dimerization and activation.  Proc Natl Acad Sci USA . 1996;  93 845-850
  • 32 DiGabriele A D, Lax I, Chen D I. Structure of a heparin-linked biologically active dimer of fibroblast growth factor.  Nature . 1998;  393 812-817
  • 33 Schlessinger J, Plotnikov A D, Hendrickson W A. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization.  Molec Cell . 2000;  6 743-750
  • 34 Cifonelli J A. Nitrous acid depolymerization of glycosaminoglycans.  Methods Carbohydr Chem . 1976;  VII 139-141
  • 35 Jaseja M, Rey R N, Sauriol F. Novel regio-and stereoselective modifications of heparin in alkaline solution. NMR spectroscopic evidences.  Can J Chem . 1989;  67 1449-1458
  • 36 Chai W, Luo J, Lim C K. Characterization of heparin oligosaccharide mixtures as ammonium salts using electrospray mass spectrometry.  Anal Chem . 1998;  70 2060-2066