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`
`Dextran and Related Polysaccharides
`
`By: Vicki Caligur, BioFiles 2008, 3.10, 17.
`Dextran
`Historically, dextrans had been long recognized as contaminants in sugar processing and other food production. The
`formation of dextran in wine was shown by Pasteur to be due to the activity of microbes.1 The name dextran was
`created by Scheibler in 1874, who demonstrated dextran was a carbohydrate with the formula (C6H10O6)n and a
`positive optical rotation.2
`
`Dextrans are polysaccharides with molecular weights ≥1,000 Dalton, which have a linear backbone of α-linked d-
`glucopyranosyl repeating units. Three classes of dextrans can be differentiated by their structural features. The
`pyranose ring structure contains five carbon atoms and one oxygen atom. Class 1 dextrans contain the α(1→6)-linked
`d-glucopyranosyl backbone modified with small side chains of d-glucose branches with α(1→2), α(1→3), and α(1→4)-
`linkage (see Figure 1). The class 1 dextrans vary in their molecular weight, spatial arrangement, type and degree of
`branching, and length of branch chains,3-5 depending on the microbial producing strains and cultivation conditions.6,7
`Isomaltose and isomaltotriose are oligosaccharides with the class 1 dextran backbone structure. Class 2 dextrans
`(alternans) contain a backbone structure of alternating α(1→3) and α(1→6)-linked d-glucopyranosyl units with α(1→3)-
`linked branches. Class 3 dextrans (mutans) have a backbone structure of consecutive α(1→3)-linked d-glucopyranosyl
`units with α(1→6)-linked branches. One and two-dimensional NMR spectroscopy techniques have been utilized for the
`structural analysis of dextrans.8
`
`Figure 1. General structure of class 1 dextrans consisting of a linear backbone of α(1→6)-linked d-glucopyranosyl repeating
`units. The dextran may have branches of smaller chains of d-glucose linked to the backbone by α(1→2)- , α(1→3)- or α(1→4)-
`glycosidic bonds.
`
`The secretion of dextrans provides an opportunity for bacteria to modulate adhesion, e.g. in tooth decay, by having a
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`Pharmacosmos A/S v. Luitpold Ex. Pharmaceuticals, Inc., IPR2015-01490
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`Luitpold Pharmaceuticals, Inc., Ex. 2023, P. 1
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`The secretion of dextrans provides an opportunity for bacteria to modulate adhesion, e.g. in tooth decay, by having a
`softer or more rigid bacterial cell surface, depending on the polysaccharide itself and the pH and ionic strength. Low
`bacterial adhesion occurs at low salt conditions with more rigid polysaccharides and a softer surface, while high
`bacterial adhesion is obtained with more flexible polysaccharides and a rigid bacterial surface. Polymer elasticity is
`important for structural integrity. and the pyranose ring is the structural unit controlling the elasticity of the
`polysaccharide. This elasticity results from a force-induced elongation of the ring structure and a final transition from a
`chair-like to a boat-like conformation of the glucopyranose ring, which plays an important role in accommodating
`mechanical stress and modulating ligand binding in biological systems.9 Laboratory experiments have demonstrated
`that cleavage of the pyranose rings of dextran, amylose, and pullulan convert these different polysaccharide chains into
`similar structures where all the bonds of the polymer backbone can rotate and align under force. After ring cleavage,
`single molecules of dextran, amylose, and pullulan display identical elastic behavior as measured by atomic force
`microscopy.
`
`Dextrans are found as bacterial extracellular polysaccharides. They are synthesized from sucrose by beneficial lactic
`acid bacteria, such as Leuconostoc mesenteroides and Lactobacillus brevis, but also by the dental plaque-forming
`species Streptococcus mutans. Bacteria employ dextran in biofilm formation10 or as protective coatings, e.g., to evade
`host phagocytes in the case of pathogenic bacteria.11
`
`The physical and chemical properties of purified dextrans vary depending on the microbial strains from which they are
`produced and by the production method, but all are white and tasteless solids. Dextrans have high water solubility and
`the solutions behave as Newtonian fluids. Solution viscosity depends on concentration, temperature, and molecular
`weight, which have a characteristic distribution.
`
`The long history of the safety of dextrans has allowed them to be used as additives to food and chemicals, and in
`pharmaceutical and cosmetics manufacturing.12 Dextrans have been investigated for the targeted and sustained
`delivery of drugs, proteins, enzymes, and imaging agents.13 In medicine, clinical grades of dextrans with a molecular
`weight range of 75-100 kDa have been used as blood-plasma volume expanders in transfusions.14 Other applications
`include the use of dextrans with polyethylene glycol as components of aqueous two-phase systems for the extraction of
`biochemicals. The hydroxyl groups present in dextran offer many sites for derivatization, and these functionalized
`glycoconjugates represent a largely unexplored class of biocompatible and environmentally safe compounds.
`
`Cross-linked dextran beads are widely used for chromatography in biochemical research and industry. The classic
`application of cross-linked dextrans is as gel filtration media in packed-bed columns for the separation and purification
`of biomolecules with molecular weights in the range of 0.7-200 kDa.15-17 Ion exchange chromatography utilizes dextran
`that has been derivatized with positively or negatively charged moieties such as carboxymethyl (CM), diethylaminoethyl
`(DEAE), diethyl(2-hydroxypropyl) aminoethyl (QAE), and sulfopropyl (SP).
`Sigma® offers a large variety of dextrans with high polydispersity and dextran molecular weight standards with low
`polydispersity (Mw/Mn values close to 1.0).
`Other Polysaccharides
`Pullulans are structural polysaccharides primarily produced from starch by the fungus Aureobasidium pullulans.18,19
`Pullulans are composed of repeating α(1→6)-linked maltotriose (D-glucopyranosyl-α(1→4)-D-glucopyranosyl-α(1→4)-D-
`glucose) units with the inclusion of occasional maltotetraose units.20 Diffusion-ordered NMR spectroscopy has been
`used to achieve a simple estimation of the molecular weight of pullulan.21 The solution properties of pullulan in water
`have been studied, and it was confirmed that pullulan molecules behave as random coils in aqueous solution.22
`Dextrins are composed of D-glucopyranosyl units but have shorter chain lengths than dextrans. They start with a single
`α(1→6) bond, but continue linearly with α(1→4)-linked D-glucopyranosyl units. Dextrins are usually mixtures derived
`from the hydrolysis of starch and have found widespread use in the food, paper, textile, and pharmaceutical industries.
`Dextran sulfates are derived from dextran via sulfation. They have become indispensable components in many
`molecular biology techniques, including the transfer of large DNA fragments from agarose gels and rapid
`hybridization,23 precipitation procedures for the quantitation of high-density lipoprotein cholesterol,24 and inhibition of
`virion binding to CD4+ cells.25
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`Materials
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` Product #
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` Image
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` Description
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` Molecular Formula
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`Add to Cart
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`Pharmacosmos A/S v. Luitpold Ex. Pharmaceuticals, Inc., IPR2015-01490
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`Luitpold Pharmaceuticals, Inc., Ex. 2023, P. 2
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`86524
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`D9885
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`30461
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`00268
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`00269
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`00270
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`00271
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`00891
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`00892
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`00893
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`00894
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`00895
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`00896
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`31394
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`31430
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`31416
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`31417
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`D9260
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`31418
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`31419
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`D1662
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`31420
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`CM-Dextran sodium salt
`BioXtra
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`DEAE-Dextran hydrochloride
`powder
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`DEAE-Dextran hydrochloride
`BioReagent, for molecular
`biology
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`Dextran analytical standard, for
`GPC, 1,000
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`Dextran analytical standard, for
`GPC, 5,000
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`Dextran analytical standard, for
`GPC, 12,000
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`Dextran analytical standard, for
`GPC, 25,000
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`Dextran analytical standard, for
`GPC, 50,000
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`Dextran analytical standard, for
`GPC, 80,000
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`Dextran analytical standard, for
`GPC, 150,000
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`Dextran analytical standard, for
`GPC, 270,000
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`Dextran analytical standard, for
`GPC, 410,000
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`Dextran analytical standard, for
`GPC, 670,000
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`Dextran enzymatic synth.
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`Dextran analytical standard, for
`GPC, Set Mp 1,000-400,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw 1,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw 5,000
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`Dextran from Leuconostoc
`mesenteroides average mol wt
`9,000-11,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw 12,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw 25,000
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`Dextran from Leuconostoc
`mesenteroides average mol wt
`35,000-45,000
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`Dextran from Leuconostoc
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`mesenteroides analytical
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`pricing
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`Pharmacosmos A/S v. Luitpold Ex. Pharmaceuticals, Inc., IPR2015-01490
`
`Luitpold Pharmaceuticals, Inc., Ex. 2023, P. 3
`
`

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`D3759
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`31421
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`D4876
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`31422
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`31423
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`31424
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`31425
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`49297
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`D5376
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`D5501
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`31397
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`31398
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`31388
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`31389
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`31390
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`09184
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`95771
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`mesenteroides analytical
`standard, for GPC, Mw 50,000
`Dextran from Leuconostoc
`mesenteroides average mol wt
`48,000-90,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw 80,000
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`Dextran from Leuconostoc
`mesenteroides average mol wt
`150,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw
`150,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw
`270,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw
`410,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw
`670,000
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`Dextran from Leuconostoc
`mesenteroides analytical
`standard, for GPC, Mw
`1,400,000
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`Dextran from Leuconostoc
`mesenteroides average mol wt
`1,500,000-2,800,000
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`Dextran from Leuconostoc
`mesenteroides industrial
`grade, average mol wt
`5,000,000-40,000,000
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`Dextran from Leuconostoc
`mesenteroides Mr ~60,000
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`Dextran from Leuconostoc
`mesenteroides Mr ~200,000
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`Dextran from Leuconostoc spp.
`Mr ~6,000
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`Dextran from Leuconostoc spp.
`Mr ~40,000
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`Dextran from Leuconostoc spp.
`Mr ~70,000
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`Dextran from Leuconostoc spp.
`Mr ~100,000
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`Dextran from Leuconostoc spp.
`Mr ~2,000,000
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`pricing
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`Pharmacosmos A/S v. Luitpold Ex. Pharmaceuticals, Inc., IPR2015-01490
`
`Luitpold Pharmaceuticals, Inc., Ex. 2023, P. 4
`
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`31392
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`31387
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`01468
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`40359
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`94504
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`68263
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`D4911
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`D6924
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`D6001
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`D8906
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`31404
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`D2006
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`D2131
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`31410
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`31414
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`Dextran from Leuconostoc spp.
`Mr ~500,000
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`Dextran from Leuconostoc spp.
`Mr 15,000-25,000
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`Dextran cross-linked G-25 50-
`150 µm particle size
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`Dextran cross-linked G-50 50-
`150 µm
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`Dextran cross-linked G-50 20-
`80 µm
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`Dextran cross-linked G-50 100-
`300 µm particle size
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`Dextran sulfate sodium salt
`from Leuconostoc spp. mol wt
`6,500-10,000
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`Dextran sulfate sodium salt
`from Leuconostoc spp.
`average mol wt 9,000-20,000
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`Dextran sulfate sodium salt
`from Leuconostoc spp.
`average mol wt >500,000
`(dextran starting material),
`contains 0.5-2.0% phosphate
`buffer, pH 6-8
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`Dextran sulfate sodium salt
`from Leuconostoc spp. for
`molecular biology, average Mw
`>500,000 (dextran starting
`material), contains 0.5-2%
`phosphate buffer
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`Dextran sulfate sodium salt
`from Leuconostoc spp. Mr
`5,000
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`Dextrin from corn Type I,
`powder
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`Dextrin from corn commercial
`grade, Type II, powder
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`Dextrin from maize starch 10
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`Dextrin from maize starch 20
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`pricing
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`Pharmacosmos A/S v. Luitpold Ex. Pharmaceuticals, Inc., IPR2015-01490
`
`Luitpold Pharmaceuticals, Inc., Ex. 2023, P. 5
`
`

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`D4894
`
`31400
`
`P4516
`
`96351
`
`
`
`
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`Dextrin from potato starch Type
`IV, powder
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`Dextrin from potato starch for
`microbiology
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`Pullulan from Aureobasidium
`pullulans suitable for substrate
`for pullulanase
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`Pullulan Standard Set set of
`analytical standards, for GPC,
`Mp 342-710′000
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`pricing
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`pricing
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`pricing
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`pricing
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`References
`
`1. Pasteur, L., Bull. Soc. Chim. Paris, 30-31 (1861).
`2. Scheibler, C., Z. Ver. Dtsch. Zucker-Ind., 24, 309-335 (1874).
`3. Robyt, J.F., in: Encyclopedia of Polymer Sci. Eng., J.I.Kroschwitz (ed.), 4, 752-767 (1986), Wiley-VCH.
`4. Cheetham, N.W.H., et al., Dextran structural details from high-field proton NMR spectroscopy. Carbohydr. Polym.
`14, 149-158 (1990).
`5. Naessens, M., et al., Leuconostoc dextransucrase and dextran: production, properties and applications. J. Chem.
`Technol. Biotechnol., 80, 845-860 (2005).
`6. Kim, D., et al., Dextran molecular size and degree of branching as a function of sucrose concentration, pH, and
`temperature of reaction of Leuconostoc mesenteroides B-512FMCM dextransucrase. Carbohydr. Res., 338, 1183-
`11889 (2003).
`7. Côté, G.L., and Leathers, T.D., A method for surveying and classifying Leuconostoc spp. glucansucrases
`according to strain-dependent acceptor product patterns. J. Ind. Microbiol. Biotechnol. 32, 53-60 (2005).
`8. Maina, N.H., et al., NMR spectroscopic analysis of exopolysaccharides produced by Leuconostoc citreum and
`Weissella confusa. Carbohydr. Res., 343, 1446-1455 (2008).
`9. Marszalek, P.E., et al., Polysaccharide elasticity governed by chair-boat transitions of the glucopyranose ring.
`Nature, 396, 661-664 (1998).
`10. Banas, J.A., and Vickermann, M.M., Glucan-binding proteins of the oral streptococci. Crit. Rev. Oral Biol. Med., 14,
`89-99 (2003).
`11. Meddens, M.J., et al., Br. J. Exp. Pathol., 65, 257-265 (1984).
`12. Kato, I., Fragrance J., 33, 59-64 (2005).
`13. Mehvar, R., Dextrans for targeted and sustained delivery of therapeutic and imaging agents. J. Controlled
`Release, 69, 1-25 (2000).
`14. Terg, R., et al., Pharmacokinetics of Dextran-70 in patients with cirrhosis and ascites undergoing therapeutic
`paracentesis. J. Hepatol., 25, 329-333 (1996).
`15. Porsch, B., and Sundelöf, L.-O., Size-exclusion chromatography and dynamic light scattering of dextrans in water:
`Explanation of ion-exclusion behaviour. J. Chromatogr. A, 669, 21-30 (1994).
`16. Neyestani, T.R., et al., Isolation of α-lactalbumin, β-lactoglobulin, and bovine serum albumin from cow’s milk using
`gel filtration and anion-exchange chromatography including evaluation of their antigenicity. Protein Expres. Purif.,
`29, 202-208 (2003).
`17. Penzol, G., et al., Use of dextrans as long and hydrophilic spacer arms to improve the performance of immobilized
`proteins acting on macromolecules. Biotechnol. Bioeng., 60, 518-523 (1998).
`18. Gibson, L.H., and Coughlin, R.W., Optimization of high molecular weight pullulan production by Aureobasidium
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`Pharmacosmos A/S v. Luitpold Ex. Pharmaceuticals, Inc., IPR2015-01490
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`Luitpold Pharmaceuticals, Inc., Ex. 2023, P. 6
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`18. Gibson, L.H., and Coughlin, R.W., Optimization of high molecular weight pullulan production by Aureobasidium
`pullulans in batch fermentations. Biotechnol. Prog., 18, 675-678 (2002).
`19. Leathers, T.D., Biotechnological production and applications of pullulan. Appl. Microbiol. Biotechnol., 62, 468-473
`(2003).
`20. Catley, B.J., Pullulan, a relationship between molecular weight and fine structure. FEBS Lett., 10, 190-193 (1970).
`21. Viel, S., et al., Diffusion-ordered NMR spectroscopy: a versatile tool for the molecular weight determination of
`uncharged polysaccharides. Biomacromolecules, 4, 1843- 1847 (2003).
`22. Nishinari, K., et al., Solution properties of pullulan. Macromolecules, 24, 5590-5593 (1991).
`23. Wahl, G.M., et al., Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and
`rapid hybridization by using dextran sulfate. Proc. Natl. Acad. Sci. USA, 76, 3683-3687 (1979).
`24. Warnick, G.R., et al., Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density-lipoprotein
`cholesterol. Clin. Chem., 28, 1379-1388 (1982).
`25. Mitsuya H., et al., Dextran sulfate suppression of viruses in the HIV family: inhibition of virion binding to CD4+
`cells. Science, 240, 646-649 (1988).
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`Pharmacosmos A/S v. Luitpold Ex. Pharmaceuticals, Inc., IPR2015-01490
`
`Luitpold Pharmaceuticals, Inc., Ex. 2023, P. 7