Sulfated oligosaccharides are involved in important biological events that are often modulated by specific sequences and sulfation patterns, but their structural analysis remains challenging. Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) analysis of three different sulfated oligosaccharides (Fondaparinux, the octasulfated pentasaccharide, a disulfated heparin-derived tetrasaccharide 1, and an octasulfated maltoheptaose) 2 was performed using the 2-(4-hydroxyphenylazo)benzoic acid-tetramethylguanidinium (HABA-TMG2) matrix. High resolution mass spectrometry of the main ions observed was successful, and this was complemented by tandem mass spectrometry (MS/MS) analysis for structural assessment. Despite sulfate losses, fully sulfated molecular ions were observed and these allowed the determination of oligosaccharide structures: UA-GlcNAc-UA(2S)-AnhMan(6S) for compound 1 and (Glc6S)6-Glc (1S,6S) for compound 2.
IozzoRV. Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem1998; 67: 609–652.
3.
CapilaILinhardtRJ. Heparin–protein interactions. Angew Chem Int Ed2002; 41: 390–412.
4.
van BoeckelCAAPetitouM. The unique antithrombin III binding domain of heparin: a lead to new synthetic antithrombotics. Angew Chem Int Ed Engl1993; 32: 1671–1690.
5.
PetitouMDuchaussoyPLedermanI, et al.Synthesis of heparin fragments. A chemical synthesis of the pentasaccharide O-(2-deoxy-2-sulfamido-6-O-sulfo-α-d-glucopyranosyl)-(1→4)-O-(β-d-glucopyranosyluronic acid)-(1→4)-O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-α-d-glucopyranosyl)-(1→4)-O-(2-O-sulfo-α-l-idopyranosyluronic acid)-(1→4)-2-deoxy-2-sulfamido-6-O-sulfo-d-glucopyranose decasodium salt, a heparin fragment having high affinity for antithrombin III. Carbohydr Res1986; 147: 221–236.
6.
PetitouMvan BoeckelCAA. A synthetic antithrombin III binding pentasaccharide is now a drug! What comes next?Angew Chem Int Ed2004; 43: 3118–3133.
7.
SchwörerRZubkovaOVTurnbullJE, et al.Synthesis of a targeted library of heparan sulfate hexa- to dodecasaccharides as inhibitors of β-secretase: potential therapeutics for Alzheimer's disease. Chem Eur J2013; 19: 6817–6823.
8.
KovenskyJGrandEUhrigMLApplications of glycosaminoglycans in the medical, veterinary, pharmaceutical, and cosmetic fields. In: GoyanesSND’AccorsoNB (eds). Industrial applications of renewable biomass products: past, present and future., 1st ed. New York, NY: Springer, 2017, pp. 135–164.
9.
KudchadkarRGonzalezRLewisKD. PI-88: a novel inhibitor of angiogenesis. Expert Opin Investig Drugs2008; 17: 1769–1776.
10.
AnastyukSDShevchenkoNMErmakovaSP, et al.Anticancer activity in vitro of a fucoidan from the brown alga Fucus evanescens and its low-molecular fragments, structurally characterized by tandem mass-spectrometry. Carbohydr Polym2012; 87: 186–194.
11.
YuanHSongJLiX, et al.Enhanced immunostimulatory and antitumor activity of diferent derivatives of κ-carrageenan oligosaccharides from Kappaphycus striatum. Appl Phycol2011; 23: 59–65.
12.
HammondEBrandtRDredgeK. PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcinoma model. PLoS One2012; 7: e52175.
13.
DredgeKHammondEHandleyP, et al.PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models. Br J Cancer2011; 104: 635–642.
14.
TangFChenFLiF. Preparation and potential in vivo anti-influenza virus activity of low molecular-weight kappa-carrageenans and their derivatives. J Appl Polym Sci2013; 127: 2110–2115.
15.
SaidJTrybalaEAnderssonE, et al.Lipophile-conjugated sulfated oligosaccharides as novel microbicides against HIV-1. Antivir Res2010; 86: 286–295.
16.
EkbladMAdamiakBBergstromT, et al.A highly lipophilic sulfated tetrasaccharide glycoside related to muparfostat (PI-88) exhibits virucidal activity against herpes simplex virus. Antivir Res2010; 86: 196–203.
17.
CoutoASSopranoLLLandoniM, et al.An anionic synthetic sugar containing 6-SO3-NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition. FEBS J2012; 279: 3665–3679.
18.
BiroccioACherfils-ViciniJAugereauA, et al.TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells. Nat Cell Biol2013; 15: 818–828.
19.
Sepulveda-DiazJEAlavi NainiSMHuynhMB, et al.HS3ST2 expression is critical for the abnormal phosphorylation of tau in Alzheimer’s disease-related tau pathology. Brain2015; 138: 1339–1354.
20.
ZhangLSongKZhouL, et al.Heparan sulfate d-glucosaminyl 3-O-sulfotransferase-3B1 (HS3ST3B1) promotes angiogenesis and proliferation by induction of VEGF in acute myeloid leukemia cells. J Cell Biochem2015; 116: 1101–1112.
21.
DelosMHellecCFoulquierF, et al.Participation of 3-O-sulfated heparan sulfates in the protection of macrophages by herpes simplex virus-1 glycoprotein D and cyclophilin B against apoptosis. FEBS Open Bio2017; 7: 133–148.
22.
HuYPLinSYHuangCY, et al.Synthesis of 3-O-sulfonated cell-surface heparan sulfate octasaccharides that inhibit herpes simplex virus type 1 host–cell interaction. Nat Chem2011; 3: 557–563.
23.
CopelandRBalasubramaniamATiwariV, et al.Using a 3-O-sulfated heparin octasaccharide to inhibit the entry of herpes simplex virus type 1. Biochemistry2008; 47: 5774–5783.
24.
StaplesGOZaiaJ. Analysis of glycosaminoglycans using mass spectrometry. Current Proteomics2011; 8: 325–336.
25.
YuGZhaoXYangB, et al.Sequence determination of sulfated carrageenan derived oligosaccharides by high-sensitivity negative-ion electrospray tandem mass spectrometry. Anal Chem2006; 78: 8499–8505.
26.
TissotBCeroniAPowellAK, et al.Software tool for the structural determination of glycosaminoglycans by mass spectrometry. Anal Chem2008; 80: 9204–9212.
27.
LiLZhangFZaiaJ, et al.Top-down approach for the direct characterization of low molecular weight heparins using LC-FT-MS. Anal Chem2012; 84: 8822–8829.
28.
ZaiaJKhatriKKleinJ, et al.Complete molecular weight profiling of low-molecular weight heparins using size exclusion chromatography-ion suppressor-high-resolution mass spectrometry. Anal Chem2016; 88: 10654–10660.
29.
BultelLLandoniMGrandE, et al.UV-MALDI-TOF mass spectrometry of heparin oligosaccharides obtained by nitrous acid controlled degradation and high performance anion exchange chromatography. J Am Soc Mass Spectrom2010; 21: 178–190.
30.
TissotBGasiunasNPowellAK, et al.Towards GAG glycomics: analysis of highly sulfated heparins by MALDI-TOF mass spectrometry. Glycobiology2007; 17: 972–982.
31.
LaremoreTNZhangFLinhardtRJ. Ionic liquid matrix for direct UV-MALDI-TOF-MS analysis of dermatan sulfate and chondroitin sulfate oligosaccharides. Anal Chem2007; 79: 1604–1610.
32.
BodetPESalardIPrzybylskiC, et al.Efficient recovery of glycosaminoglycan oligosaccharides from polyacrylamide gel electrophoresis combined with mass spectrometry analysis. Anal Bioanal Chem2017; 409: 1257–1269.
33.
ArmstrongDWZhangLKHeL, et al.Ionic liquids as matrixes for matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem2001; 73: 3679–3686.
34.
PrzybylskiCGonnetFBonnafféD, et al.HABA-based ionic liquid matrices for UV-MALDI-MS analysis of heparin and heparan sulfate oligosaccharides. Glycobiology2010; 20: 224–234.
35.
LesurDGassamaAMoreauV, et al.Synthesis of regioselectively and uniformly modified maltoheptaose derivatives from cyclomaltoheptaose precursors. Carbohydr Res2005; 340: 1225–1231.
36.
DomonBCostelloCA. Systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates. Glycoconj J1988; 5: 397–409.
37.
CasuB. Structure and biological activity of heparin. Adv Carbohydr Chem Biochem1985; 43: 51–132.
PoyerSLopin-BonCJacquinetJC, et al.Isomer separation and effect of the degree of polymerization on the gas-phase structure of chondroitin sulfate oligosaccharides analyzed by ion mobility and tandem mass spectrometry. Rapid Commun Mass Spectrom2017; 31: 2003–2010.
