Abstract
We have prepared a number of isomeric red seaweed galactan-derivative sulfated oligosaccharides to determine whether there were diagnostic differences among the isomeric mass spectra obtained using ESI CID MS/MS (triple quadrupole instrument). Fragmentation of the single or multicharged molecular ions from di-, tetra-, and hexasaccharides indicated that the relative positioning of the sulfate groups and type of monosaccharide unit affect the rate of cleavage of the glycosidic bonds. We also performed a comparative [M-Na]− fragmentation study of positional isomers of sulfated disaccharides that present all four monosulfation possibilities on the galactopyranosidic ring. In this case, negative-ion ESI CID MS/MS approach gave diagnostic product ions from cross-ring cleavages along with the same main B1 ion (from sulfated Galp), at m/z 241, for all isomers. The isomeric disaccharides were also submitted to increased spray energy conditions inducing in-source fragmentation; preformed B1 ions were then fragmented to give similar product ions as those found in [M-Na]− analysis. Evaluation of the relative abundances mainly for cross-ring fragment ions at m/z 138, 139, 151, 153 allowed clear distinction among the members of the disaccharide series. The different ratios for m/z 151/153 ions were consistent with the predominance of m/z 153 being related to the cases when the bond involved in the cleavage process links a sulfated carbon. A quadrupole ion trap instrument (MSn analysis) was also utilized to compare the results obtained with the triple quadrupole instrument.
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Laabs, T.; Carulli, D.; Geller, H. M.; Fawcett, J. W. Chondroitin Sulfate Proteoglycans in Neural Development and Regeneration. Curr. Opin. Neurobiol. 2005, 15, 116–120.
Sasisekharan, R.; Shriver, Z.; Venkataraman, G.; Narayanasami, U. Roles of Heparan-Sulphate Glycosaminoglycans in Cancer. Nat. Rev. Cancer. 2002, 2, 521–528.
Yip, G. W.; Smollich, M.; Gotte, M. Therapeutic Value of Glycosaminoglycans in Cancer. Mol. Cancer Ther. 2006, 5, 2139–2148.
Capila, I.; Linhardt, R. J. Heparin-Protein Interactions. Angew. Chem. Int. Ed. 2002, 41, 391–412.
Kisilevsky, R.; Ancsin, J. B.; Szarek, W. A.; Petanceska, S. Heparan Sulfate as a Therapeutic Target in Amyloidogenesis: Prospects and Possible Complications. Amyloid 2007, 14, 21–32.
Gama, C. I.; Hsieh-Wilson, L. C. Chemical Approaches to Deciphering the Glycosaminoglycan Code. Curr. Opin. Chem. Biol. 2005, 9, 609–619.
Gama, C. I.; Tully, S. E.; Sotogaku, N.; Clark, P. M.; Rawat, M.; Vaidehi, N.; Goddard, W. A. III; Nishi, A.; Hsieh-Wilson, L. C. Sulfation Patterns of Glycosaminoglycans Encode Molecular Recognition and Activity. Nat. Chem. Biol. 2006, 2, 467–473.
Thomsson, K. A.; Karlsson, N. G.; Hansson, G. C. Liquid Chromatography-electrospray Mass Spectrometry as a Tool for the Analysis of Sulfated Oligosaccharides from Mucin Glycoproteins. J. Chromatogr. A 1999, 854, 131–139.
Thomsson, K. A.; Karlsson, H.; Hansson, G. C. Sequencing of Sulfated Oligosaccharides from Mucins by Liquid Chromatography and Electrospray Ionization Tandem Mass Spectrometry. Anal. Chem. 2000, 72, 4543–4549.
Ekeberg, D.; Knutsen, S. H.; Sletmoen, M. Negative-Ion Electrospray Ionization-mass Spectrometry (ESI-MS) as a Tool for Analyzing Structural Heterogeneity in K-carrageenan Oligosaccharides. Carbohydr. Res. 2001, 334, 49–59.
Zaia, J.; Costello, C. E. Compositional Analysis of Glycosaminoglycans by Electrospray Mass Spectrometry. Anal. Chem. 2001, 73, 233–239.
Zaia, J.; Costello, C. E. Tandem Mass Spectrometry of Sulfated Heparin-Like Glycosaminoglycan Oligosaccharides. Anal. Chem. 2003, 75, 2445–2455.
Lamb, D. J.; Wang, H. M.; Mallis, L. M.; Linhardt, R. J. Negative Ion Fast-Atom Bombardment Tandem Mass Spectrometry to Determine Sulfate and Linkage Position in Glycosaminoglycan-derived Disaccharides. J. Am. Soc. Mass Spectrom. 1992, 3, 797–803.
Linhardt, R. J.; Wang, H. M.; Loganathan, D.; Lamb, D. J.; Mallis, L. M. Analysis of Glycosaminoglycan-derived Oligosaccharides Using Fast-Atom-Bombardment Mass-Spectrometry. Carbohydr. Res. 1992, 225, 137–145.
Fukuyama, Y.; Ciancia, M.; Nonami, H.; Cerezo, A. S.; Erra-Balsells, R.; Matulewicz, M. C. Matrix-Assisted Ultraviolet Laser-Desorption Ionization and Electrospray-Ionization Time-of-Flight Mass Spectrometry of Sulfated Neocarrabiose Oligosaccharides. Carbohydr. Res. 2002, 337, 1553–1562.
Laremore, T. N.; Zhang, F.; Linhardt, R. J. Ionic Liquid Matrix for Direct UV-MALDI-TOF-MS Analysis of Dermatan Sulfate and Chondroitin Sulfate Oligosaccharides. Anal. Chem. 2007, 79, 1604–1610.
Yu, G.; Zhao, X.; Yang, B.; Ren, S.; Guan, H.; Zhang, Y.; Lawson, A. M.; Chai, W. Sequence Determination of Sulfated Carrageenan-Derived Oligosaccharides by High-Sensitivity Negative-ion Electrospray Tandem Mass Spectrometry. Anal. Chem. 2006, 78, 8499–8505.
Gunay, N. S.; Tadano-Aritomi, K.; Toida, T.; Ishizuka, I.; Linhart, R. J. Evaluation of Counterions for Electrospray Ionization Mass Spectral Analysis of a Highly Sulfated Carbohydrate, Sucrose Octasulfate. Anal. Chem. 2003, 75, 3226–3231.
Saad, O. M.; Leary, J. A. Compositional Analysis and Quantification of Heparin and Heparan Sulfate by Electrospray Ionization Ion Trap Mass Spectrometry. Anal. Chem. 2003, 75, 2985–2995.
Saad, O. M.; Leary, J. A. Delineating Mechanisms of Dissociation for Isomeric Heparin Disaccharides Using Isotope Labeling and Ion Trap Tandem Mass Spectrometry. J. Am. Soc. Mass Spectrom. 2004, 15, 1274–1286.
Yu, G.; Guan, H.; Ioanoviciu, A. S.; Sikkander, S. A.; Thanawiroon, C.; Tobacman, J. K.; Toida, T.; Linhardt, R. J. Structural Studies on κ-Carrageenan Derived Oligosaccharides. Carbohydr. Res. 2002, 337, 433–440.
Korir, A. K.; Limtiaco, J. F.; Gutierrez, S. M.; Larive, C. K. Ultraperformance Ion-Pair Liquid Chromatography Coupled to Electrospray Time-of-Flight Mass Spectrometry for Compositional Profiling and Quantification of Heparin and Heparan Sulfate. Anal. Chem. 2008, 80, 1297–1306.
Meissen, J. K.; Sweeney, M. D.; Girardi, M.; Lawrence, R.; Esko, J. D.; Leary, J. A. Differentiation of 3-O-Sulfatated Heparin Disaccharide Isomers: Identification of Structural Aspects of the Heparin CCL2 Binding Motif. J. Am. Soc. Mass Spectrom. 2009, 20, 652–657.
Mason, K. E.; Meikle, P. J.; Hopwood, J. J.; Fuller, M. Characterization of Sulfated Oligosaccharides in Mucopolysaccharidosis Type MA by Electrospray Ionization Mass Spectrometry. Anal. Chem. 2006, 78, 4534–4542.
Zaia, J.; McClellan, J. E.; Costello, C. E. Tandem Mass Spectrometric Determination of the 4S/6S Sulfation Sequence in Chondroitin Sulfate Oligosaccharides. Anal. Chem. 2001, 73, 6030–6039.
McClellan, J. M.; Costello, C. E.; O’Connor, P. B.; Zaia, J. Influence of Charge State on Product Ion Mass Spectra and the Determination of 4S/6S Sulfation Sequence of Chondroitin Sulfate Oligosaccharides. Anal. Chem. 2002, 74, 3760–3771.
Zaia, T.; Li, X. Q.; Chan, S. Y.; Costello, C. E. Tandem Mass Spectrometric Strategies for Determination of Sulfation Positions and Uronic Acid Epimerization in Chondroitin Sulfate Oligosaccharides. J. Am. Soc. Mass Spectrom. 2003, 14, 1270–1281.
Tissot, B.; Salpin, J.-Y.; Martinez, M.; Gaigeot, M.-P.; Daniel, R. Differentiation of the Fucoidan Sulfated L-Fucose Isomers Constituents by CE-ESIMS and Molecular Modeling. Carbohydr. Res. 2006, 341, 598–609.
Ii, T.; Okuda, S.; Hirano, T.; Ohashi, M. Tandem Mass Spectrometry for Characterization of Unsaturated Disaccharides from Chondroitin Sulfate, Dermatan Sulfate, and Hyaluronan. Glycoconj. J. 1994, 11, 123–132.
Liu, R. H.; Chanthamontri, C.; Han, H. L.; Han, H.; Hernández-Torres, J. M.; Wood, K. V.; McLuckey, S. A.; Wei, A. Solid-Phase Synthesis of α-Glucosamine Sulfoforms with Fragmentation Analysis by Tandem Mass Spectrometry. J. Org. Chem. 2008, 73, 6059–6072.
Gonçalves, A. G.; Ducatti, D. R. B.; Duarte, M. E. R.; Noseda, M. D. Sulfated and Pyruvylated Disaccharide Alditols Obtained from a Red Seaweed Galactan: ÈSIMS and NMR Approaches. Carbohydr. Res. 2002, 337, 2443–2453.
Antonopoulos, A.; Favetta, P.; Helbert, W.; Lafosse, M. Isolation of α-Carrageenan Oligosaccharides Using Ion-Pair Liquid Chromatography — Characterization by Electrospray Ionization Mass Spectrometry in Positive-Ion Mode. Carbohydr. Res. 2004, 339, 1301–1309.
Antonopoulos, A.; Favetta, P.; Helbert, W.; Lafosse, M. On-Line Liquid Chromatography Electrospray Ionization Mass Spectrometry for the Characterization of κ- and ι-Carrageenans. Application to the Hybrid ι/ν Carrageenans. Anal. Chem. 2005, 77, 4125–4136.
Gonçalves, A. G.; Ducatti, D. R. B.; Paranha, R. G.; Duarte, M. E. R.; Noseda, M. D. Positional Isomers of Sulfated Oligosaccharides Obtained from Agarans and Carrageenans: Preparation and Capillary Electrophoresis Separation. Carbohydr. Res. 2005, 340, 2123–2134.
Aguilan, J. T.; Dayrit, F. M.; Zhang, T.; Ninonuevo, M. R.; Lebrilla, C. B. Structural Analysis of κ-Carrageenan Sulfated Oligosaccharides by Positive Mode Nano-ESI-FTICR-MS and MS/MS by SORI-CID. J. Am. Soc. Mass Spectrom. 2006, 17, 96–103.
Antonopoulos, A.; Favetta, P.; Helbert, W.; Lafosse, M. On-Line Liquid Chromatography-electrospray Ionisation Mass Spectrometry for κ-Carrageenan Oligosaccharides with a Porous Graphitic Carbon Column. J. Chromatogr. A 2007, 1147, 37–41.
Yang, B.; Yu, G. L.; Zhao, X.; Jiao, G. L.; Ren, S. M.; Chai, W. G. Mechanism of Mild Acid Hydrolysis of Galactan Polysaccharides with Highly Ordered Disaccharide Repeats Leading to a Complete Series of Exclusively Odd-Numbered Oligosaccharides. FEBS J. 2009, 276, 2125–2137.
Painter, T. J. Algal Polysaccharides. In The Polysaccharides, Aspinall, G. O., Ed., Academic Press: New York, 1983; p. 195.
De Ruiter, G. A.; Rudolph, B. Carrageenan Biotechnology. Trends Food. Sci. Technol. 1997, 8, 389–95.
Usov, A. I. Structural Analysis of Red Seaweed Galactans of Agar and Carrageenan Groups. Food Hydrocoll. 1998, 12, 301–308.
Ciancia, M.; Noseda, M. D.; Matulewicz, M. C.; Cerezo, A. S. Alkali-Modification of Carrageenans: Mechanism and Kinetics in the κ/ ι−, μ/ ν −, and λ-series. Carbohydr. Polym. 1993, 20, 95–98.
Noseda, M. D.; Cerezo, A. S. Alkali Modification of Carrageenans. II. The Cyclization of Model Compounds Containing Nonsulfated β-D-Galactose Units. Carbohydr. Polym. 1995, 26, 1–3.
Noseda, M. D.; Viana, A. G.; Duarte, M. E. R.; Cerezo, A. S. Alkali Modification of Carrageenans. Part I. V. Porphyrans as Model Compounds. Carbohydr. Polym. 2000, 42, 301–305.
Viana, A. G.; Noseda, M. D.; Duarte, M. E. R.; Cerezo, A. S. Alkali Modifications of Carrageenans. Part V. The ι-í Hybrid Carrageenan from Euckeuma denticulatum and its Cyclization to ι-Carrageenan. Carbohydr. Polym. 2004, 58, 455–460.
Zibetti, R. G. M.; Noseda, M. D.; Cerezo, A. S.; Duarte, M. E. R. The System of Galactans from Cryptonemia crenulata (Halymeniaceae, Halymeniales) and the Structure of Two Major Fractions. Kinetic Studies on the Alkaline Cyclization of the Unusual Diad G2S → D(L)6S. Carbohydr. Res. 2005, 340, 711–722.
Carlucci, M. J.; Pujol, C. A.; Ciancia, M.; Noseda, M. D.; Matulewicz, M. C.; Damonte, E. B.; Cerezo, A. S. Antiherpetic and Anticoagulant Properties of Carrageenans from the Red Seaweed Gigartina skottsbergii and their Cyclized Derivatives: Correlation Between Structure and Biological Activity. Int. J. Biol. Macromol. 1997, 20, 97–105.
Duarte, M. E. R.; Noseda, D. G.; Noseda, M. D.; Tulio, S.; Pujol, C. A.; Damonte, E. B. Inhibitory Effect of Sulfated Galactans from the Marine Alga Bostrychia montagnei on Herpes Simplex Virus Replication In Vitro. Psytomedicine 2001, 8, 53–58.
Duarte, M. E. R.; Cauduro, J. P.; Noseda, D. G.; Noseda, M. D.; Gonçalves, A. G.; Pujol, C. A.; Damonte, E. B.; Cerezo, A. S. The Structure of the Agaran Sulfate from Acanthophora spicifera (Rhodomelaceae, Ceramiales) and Its Antiviral Activity. Relation Between Structure and Antiviral Activity in Agarans. Carbohydr. Res. 2004, 339, 335–347.
Talarico, L. B.; Zibetti, R. G. M.; Faria, P. C. S.; Scolaro, L. A.; Duarte, M. E. R.; Noseda, M. D.; Pujol, C. A.; Damonte, E. B. Anti-Herpes Simplex Virus Activity of Sulfated Galactans from the Red Seaweeds Gymnogongrus griffithsiae and Cryptonemia crenulata. Int. J. Biol. Macromol. 2004, 34, 63–71.
Harden, E. A.; Falshaw, R.; Carnachan, S. M.; Kern, E. R.; Prichard, M. N. Virucidal Activity of Polysaccharide Extracts from Four Algal Species Against Herpes Simplex Virus. Antivir. Res. 2009, 83, 282–289.
Talarico, L. B.; Damonte, E. B. Interference in Dengue Virus Adsorption and Uncoating by Carrageenans. Virology 2007, 363, 473–485.
Talarico, L. B.; Pujol, C. A.; Zibetti, R. G. M.; Faria, P. C. S.; Noseda, M. D.; Duarte, M. E. R.; Damonte, E. B. The Antiviral Activity of Sulfated Polysaccharides Against Dengue Virus is Dependent on Virus Serotype and Host Cell. Antivir. Res. 2005, 66, 103–110.
De S. F.; Tisher, P. C.; Talarico, L. B.; Noseda, M. D.; Guimarães, S. M. P. B.; Damonte, E. B.; Duarte, M. E. R. Chemical Structure and Antiviral Activity of Carrageenans from Meristiella gelidium Against Flerpes Simplex and Dengue Virus. Carbohydr. Polym. 2006, 63, 459–465.
Ghosh, T.; Chattopadhyay, K.; Marschall, M.; Karmakar, P.; Mandal, P.; Ray, B. Focus on Antivirally Active Sulfated Polysaccharides: From Structure-activity Analysis to Clinical Evaluation. Glycobiology 2009, 19, 2–15.
Gonçalves, A. G.; Noseda, M. D.; Duarte, M. E. R.; Grindley, T. B. Semi-synthesis of a 3-O-sulfated Red Seaweed Galactan-Derived Disaccharide Alditol. Carbohydr. Res. 2006, 341, 1753–1757.
Domon, B.; Costello, C. E. A Systematic Nomenclature for Carbohydrate Fragmentations in FAB-MS/MS Spectra of Glycoconjugates. Glycoconj. J. 1988, 5, 397–409.
Matulewicz, M. C.; Ciancia, M.; Noseda, M. D.; Cerezo, A. S. Methylation Analysis of Carrageenans from Tetrasporic and Cystocarpic Stages of Gigartina skottsbergii. Phytochemistry 1990, 29, 3407–3410.
Guimarães, M.; Viana, A. G.; Duarte, M. E. R.; Ascêncio, S. D.; Plastino, E. M.; Noseda, M. D. Low-Molecular-Mass Carbohydrates and Soluble Polysaccharides of Green and Red Morphs of Gracilaria domingensis (Gracilariales, Rhodophyta). Bot. Mar. 2007, 50, 314.
Usov, A. I.; Elashvili, M. Polysaccharides of Algae 44. Investigation of Sulfated Galactan from Laurencia nipponica Yamada (Rhodophyta, Rhodomelaceae), Using Partial Reductive Hydrolysis. Bot. Mar. 1991, 34, 553–560.
Gonçalves, A. G.; Noseda, M. D.; Duarte, M. E. R.; Grindley, T. B. Semi-Synthesis of Long Chain Alkyl Ether Derivatives of Sulfated Oligosaccharides Via Dibutylstannylene Acetal Intermediates. J. Org. Chem. 2007, 72, 9896–9904.
Falshaw, R.; Furneaux, R. H. The Structural Analysis of Disaccharides from Red Algal Galactans by Methylation and Reductive Partial-hydrolysis. Carbohydr. Res. 1995, 269, 183–189.
Usov, A. I.; Elashvili, M. Polysaccharides from Algae. 51. Partial Reductive Hydrolysis of Sulfated Galactan from Red Alga Laurencia coronopus J. Ag. (Rhodophyta, Rhodomelaceae). Russ. J. Bioorg. Ckem. 1997, 23, 468–173.
Falshaw, R.; Furneaux, R. H.; Wong, H. Analysis of Pyruvylated β-Carrageenan by 2D NMR Spectroscopy and Reductive partial Hydrolysis. Carbohydr. Res. 2003, 338, 1403–1414.
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Gonçalves, A.G., Ducatti, D.R.B., Grindley, T.B. et al. ESI-MS differential fragmentation of positional isomers of sulfated oligosaccharides derived from carrageenans and agarans. J Am Soc Mass Spectrom 21, 1404–1416 (2010). https://doi.org/10.1016/j.jasms.2010.03.045
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DOI: https://doi.org/10.1016/j.jasms.2010.03.045