Altered immunomodulating and toxicological properties of degraded Quillaja saponaria Molina saponins

Marciani, Dante J.; Pathak, Ashish; Reynolds, Robert C.; Seitz, Lainne E.; May, Richard

doi:10.1016/s1567-5769(01)00016-9

Cited by 70 publications

(49 citation statements)

References 18 publications

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“…[18] The fatty acyl chains seem to play a critical role in immune stimulation, as derived from deacylated saponin DS-1 obtained via alkaline hydrolysis of saponin QS 21. [11,15,21,22] Strong alkaline hydrolysis of DS-1 yielded QS- L1. [10] This molecule was demonstrated to greatly increase both humoral immunity and cellular immune response when administered in the presence of alum-precipitated recombinant hepatitis B surface antigen.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Saponins with Cholestanol, Cholesterol, and Friedelanol as Aglycones

et al. 2006

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Procedures for the synthesis of branched Xylβ(1→3)[Galβ(1→2)]‐Glc and Xylβ(1→3)[Galβ(1→2)]‐GlcUA trisaccharides β‐linked to the 3‐O of cholesterol, cholestanol, and friedelanol, respectively, were developed. To this end, β‐selective glucosylation of cholesterol with glucosyl donors giving selective access to 2‐O, 3‐O, and 6‐O was studied. This way intermediates 10 and 21 having 2‐O‐acyl, 3‐O‐benzyl and 4,6‐O‐benzylidene or also benzyl protection were obtained. Removal of the 2‐O‐acyl group and then galactosylation afforded β(1→2)‐linked disaccharide intermediates 14 and 23. Standard manipulations with the O‐benzylidene and/or O‐benzyl protecting groups gave selective access to the 3‐O of the glucosyl residue, thus affording with a xylosyl donor the trisaccharide β‐linked to the cholesteryl residue (compound 18) as decisive intermediate. Also an alternative procedure to this compound via attachement of a Xylβ(1→3)Glc residue to cholesterol and then galactosylation could be developed. Total deprotection of 18 or regioselective introduction of a sulfate group and of a dodecylcarbamoyl residue at 6a‐O furnished saponins 34, 36, and 38, respectively. Hydrogenation of cholesteryl disaccharide 23 led directly to a 3a‐O‐unprotected cholestanyl disaccharide 39. β‐Selective xylosylation and transformation of the liberated glucose hydroxymethyl group into a carboxylic group afforded target molecule 1b having the desired Xyl(1→3)[Gal(1→2)]‐GlcUA β‐linked to cholestanol. Similarly, a saponin analog was obtained having an α‐linked L‐rhamnosyl residue instead of the β‐linked D‐xylosyl residue. Application of the glycosylation sequence, as worked out for cholesterol, to friedelanol led to attachment of the Xylβ(1→3)[Galβ(1→2)]‐Glc residue to the 3‐O (compound 54). Complete O‐deacylation led to saponin 55; oxidation of the hydroxymethyl group of the glucose residue to the carboxylic group and then deprotection afforded target molecule 2 containing the same trisaccharide residue as 1b. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Section: Introductionmentioning

confidence: 99%

Synthesis of Saponins with Cholestanol, Cholesterol, and Friedelanol as Aglycones

et al. 2006

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“…Several potential adjuvants are in various stages of research and development including monophosphoryl lipid A (20), CpG oligonucleotides (25), saponins (26), and lipid vesicles (10). One of the most significant limitations to these preparations, besides their often severe side effects (24), are their structural constraints, where small modifications of the base structure result in either increased toxicity or decreased efficacy (15).…”

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confidence: 99%

Adjuvant Activity of Emulsan, a Secreted Lipopolysaccharide from Acinetobacter calcoaceticus

Panilaitis

Johri

Blank

et al. 2002

Clin Vaccine Immunol

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Several promising adjuvant candidates have been studied over the past 75 years; however, only alum is currently approved for human use. The complex acylated polysaccharide emulsan, secreted from Acinetobacter calcoaceticus, represents a new candidate. Unique features of this family of polymers are their amenability to structural tailoring and their emulsification behavior. We demonstrate that emulsan activates macrophages in a dose-dependent manner. This activation is dependent on the presence of the fatty acid side chains that decorate the polysaccharide backbone, and, furthermore, the level of activation can be affected by changes in the chemical characteristics of emulsan structural variants. One emulsan variant was examined in a classical hapten carrier immunization protocol and demonstrated significant adjuvant activity as determined by haptenspecific antibody titers. This immune response was characterized by a high immunoglobulin G2a titer, consistent with a Th1 response. The significant immunopotentiation demonstrated by this complex polymer establishes emulsan as an exciting new candidate adjuvant. Furthermore, by manipulating the chemical structure of this compound, we can explore the physical basis of pattern recognition receptors and macrophage activation.Taking its name from the Latin word adjuvare, which means to help, an adjuvant is any compound that increases the strength and/or duration of an immune response to a foreign antigen over that caused by the antigen alone (19). The important characteristics of an adjuvant are its ability to enhance the immune response to the target antigen, long-term safety in widespread application, and flexibility in its use for different antigen and disease systems.Since its adjuvant activity was first described over 75 years ago (6), alum remains the only adjuvant approved for use in humans (5). Several potential adjuvants are in various stages of research and development including monophosphoryl lipid A (20), CpG oligonucleotides (25), saponins (26), and lipid vesicles (10). One of the most significant limitations to these preparations, besides their often severe side effects (24), are their structural constraints, where small modifications of the base structure result in either increased toxicity or decreased efficacy (15).Emulsan is a complex extracellular acylated polysaccharide produced by the gram-negative bacterium Acinetobacter calcoaceticus, which is ubiquitous in nature and which is considered to be part of the normal human commensal load (3, 4). Emulsan has been extensively researched for its industrial applications as an emulsifier (7-9, 13, 21, 27, 28). This molecule is composed of an unbranched polysaccharide backbone with O-acyl and N-acyl bound fatty acid side chains. The polysaccharide backbone consists of three aminosugars, D-galactosamine, D-galactosaminouronic acid, and a dideoxydiaminohexose in the ratio 1:1:1 (2, 9). The fatty acid side chains range in length from 10 to 22 carbons and can represent from 5 to 23% (wt/wt) of the polymer. The emu...

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“…They have the unique capacity to stimulate both the Th1 immune response and the production of cytotoxic T cells against exogenous antigens, making them ideal for the vaccines against intracellular pathogens [12]. However, the application of Quillaja saponins is limited to human vaccination because of high toxicity and unstability in aqueous phase [6,15].…”

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confidence: 99%

“…Although both QS-18 and QS-21 were the saponin components of Quil-A and were equally active, the former was much more lethal in mice [2]. The structure modification of Quillaja saponins resulted in the altereation of immunomodulating and toxicological properties [5,6].…”

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confidence: 99%

Starfish, Asterias amurensis and Asterina pectinifera, as Potential Sources of Th1 Immunity-Stimulating Adjuvants

Kawase¹,

Goo

Jujo

et al. 2011

The Journal of Veterinary Medical Science

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ABSTRACT. Saponin is the generic name of steroid or triterpene glycosides, and the capacities of some saponins to stimulate both Th1 immune response and production of cytotoxic T cells are useful as vaccine components against intracellular pathogens. Because saponins have been found commonly in starfish, we assessed the potential of starfish, Asterias amurensis and Asterina pectinifera, as adjuvant sources. Crude starfish saponins had hemolytic activities (EC 50 =10 to 100 μg/ml) and thin layer chromatography indicated heterogeneity of their constituents. When starfish saponis were subcutaneously injected into mice with ovalbumin (OVA), OVA-specific IgG, especially IgG2a instead of IgG1 was produced in mouse blood, suggesting starfish saponins stimulated Th1 type immunity and they were potential sources of new adjuvants.

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Altered immunomodulating and toxicological properties of degraded Quillaja saponaria Molina saponins

Cited by 70 publications

References 18 publications

Synthesis of Saponins with Cholestanol, Cholesterol, and Friedelanol as Aglycones

Synthesis of Saponins with Cholestanol, Cholesterol, and Friedelanol as Aglycones

Adjuvant Activity of Emulsan, a Secreted Lipopolysaccharide from Acinetobacter calcoaceticus

Starfish, Asterias amurensis and Asterina pectinifera, as Potential Sources of Th1 Immunity-Stimulating Adjuvants

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