Development of natural product (1 → 3)‐β‐<scp>D</scp>‐glucan polymers as immune‐stimulating pharmaceuticals

Williams, David L.; Browder, I. William

doi:10.1002/pat.1994.220050910

Cited by 10 publications

(6 citation statements)

References 28 publications

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“…The glucans obtained are particles with diameters in the l m range which are insoluble in water 17) . This is acceptable in applications such as ointments or skin creams for treating wounds.…”

Section: Derivatization Of Glucansmentioning

confidence: 99%

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Polymer analytical characterization of glucan and mannan from yeast Saccharomyces cerevisiae

Kath

Kulicke²

1999

Angew. Makromol. Chem.

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SUMMARY: Samples of glucans and mannans isolated from yeast, Saccharomyces cerevisiae, were characterized using polymer analytical methods:13 C and 1 H NMR spectroscopy, IR spectroscopy and light scattering coupled with size exclusion chromatography (SEC/MALLS). Despite partially incomplete reactions, high-molar-mass mannans with a trimodal distribution were obtained with all the enzyme systems. Mannoprotein with a molar mass of 410 000 g mol -1 was obtained using a recombinant glucanase that was completely void of protease activity.Chemically extracted mannans had molar masses of 21 000 -62 000 g mol -1, whereas enzymatically isolated mannans had molar masses between 64 000 and 112 000 g mol -1. The native structure of the mannans was damaged by acids and alkalis in chemical extraction. Mannans that were isolated with protease after 6 -7 h had molar masses from 116 000 -190 000 g mol -1. Here the protein matrix was not completely hydrolysed. Glucan exhibited the 6 signals of the ring C atoms in the 13 C NMR spectrum, and in the IR spectrum the typical mannan bands at 820 cm -1 had disappeared. The degree of substitution of the synthesized CM-glucans (CM = carboxymethyl), which was determined by 13 C NMR spectroscopy, had values ranging from DS = 0.5 -1. In curdlan derivatives, depending upon the synthesis, over 90% degradation was found for the phosphatization, whereas in the carboxymethylation of barley glucan the degradation was only 15 -35%.The glucan derivatives of the baker's yeast investigated have higher molar masses than those of the spent brewer's yeast investigated. CM-glucans synthesized from yeast had a bimodal distribution. This was not observed for CM-curdlan. Reacting the cell walls with an enzyme cocktail (EC3) at pH = 9 was intended to suppress the glucanase activity in favour of protease activity, so as to achieve high-molar-mass glucan. However, the molar masses of 65 000 -100 000 g mol -1 from the CM-glucans synthesized in this way showed that the glucanase activity could only be partially suppressed. , während enzymatisch isolierte Mannane Molmassen zwischen 64 000 und 112 000 g mol -1 hatten. Durch Säuren oder Laugen wurde bei der chemischen Extraktion die native Struktur des Mannans beschädigt. Mannane, die mit Protease nach 6 -7 h isoliert wurden, hatten Molmassen von 116 000 -190 000 g mol -1. Hier wurde die Protein-Matrix noch nicht vollständig hydrolysiert.Glucan zeigte im 13 C-NMR-Spektrum die 6 Signale der Ring-C-Atome, und im IR-Spektrum war die typische Mannan-Bande bei 820 cm -1 verschwunden. Der durch 13 C-NMR-Spektroskopie bestimmte Substitutionsgrad DS der hergestellten wasserlöslichen Carboxymethyl(CM)-Glucane lag bei DS = 0,5 -1. Am Beispiel von Curdlanderivaten wurde für die Phosphatierung eine synthesebedingte Degradation von über 90% nachgewiesen, während bei der Carboxymethylierung von Gerstenglucan die Degradation nur 15 -35% betrug.Die Glucanderivate der untersuchten Bäckerhefe haben höhere Molmassen als die der untersuchten Brauereiüberschußhefe. CM-Glucane, die aus He...

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Section: Derivatization Of Glucansmentioning

confidence: 99%

“…Furthermore, interaction with immune cells is restricted to only the external surface of the particles. Syntheses have therefore been developed in which the insoluble yeast glucans are transformed into soluble derivatives [17][18][19][20][21][22] .…”

Section: Derivatization Of Glucansmentioning

confidence: 99%

Polymer analytical characterization of glucan and mannan from yeast Saccharomyces cerevisiae

Kath

Kulicke²

1999

Angew. Makromol. Chem.

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“…Numerous in vitro tests on isolated immune cells as well as in vivo tests on mice, rats and higher mammals have in some cases demonstrated a stronger stimulating effect of the glucan 6,8) . b -1,3-D-glucan from the cell wall of baker's yeast (Saccharomyces cerevisiae), in particular, exhibits a strongly stimulating effect 9) . This glucan is extracted chemically.…”

Section: Introductionmentioning

confidence: 99%

“…This glucan is extracted chemically. However, as it is insoluble in water, numerous procedures for manufacturing a water-soluble derivative have been developed 10) , which have enabled side-effects to be eliminated and the activity to be increased 9) . One side-effect of the process of glucan extraction is the release of mannan, for which there is also documentary evidence of an immunomodulatory potential [11][12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Mild enzymatic isolation of mannan and glucan from yeast Saccharomyces cerevisiae

Kath

Kulicke²

1999

Angew. Makromol. Chem.

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SUMMARY: An enzymatic procedure to isolate polysaccharides from the yeast saccharomyces cerevisiae was developed which would both be environmentally friendly and preserve the native structure of the polymers. Two proteases and three enzyme cocktails were employed.To isolate the cell wall polysaccharides, the cell walls were first separated from the internal components by mechanical cell disruption. The quality of cell disruption was investigated for four types of glass beads with diameters from 0.25 -1.5 mm and monitored via the inner cellular proteins released. With large glass beads (Ø = 0.75 -1.5 mm) both brewer's and baker's yeast cells exhibited more than 90% cell disruption after as little as 12 min, whereas disruption was still incomplete with smaller beads. The isolated cell wall material was purified on microporous membranes, freeze-dried and then incubated with enzymes. Proteases caused protein lysis in the outer cell wall and released soluble mannan. The insoluble glucan was separated by centrifugation and the mannan was purified by dialysis or chromatography.In the digestion with proteases, complete conversion was achieved at concentrations higher than 240 mg g -1 of cell wall material within 26 h. Cell walls from baker's yeast had to undergo a preliminary extraction with petroleum ether. Complete conversion was only possible with one of the enzyme cocktails investigated, and this was achieved after as little as 6 h for cell walls from both baker's and brewer's yeast. The activity of the two other enzyme cocktails investigated was weaker, with brewer's yeast cell walls generally reacting more readily than those of baker's yeast. ZUSAMMENFASSUNG: Im Hinblick auf die Entwicklung umweltfreundlicher Verfahren und den Schutz der nativen Polymerstruktur wurde ein enzymatisches Verfahren zur Isolierung von Polysacchariden aus derHefe Saccharomyces cerevisiae entwickelt. Eingesetzt wurden zwei Proteasen sowie drei Enzymcocktails.Zur enzymatischen Gewinnung der Zellwand-Polysaccharide wurden zunächst die Zellwände durch einen mechanischen Zellaufschluß vom Zellinneren getrennt. Die Aufschlußgüte wurde für vier Glasperlensorten mit Durchmessern von 0,25 -1,5 mm untersucht und anhand der freigesetzten innerzellulären Proteine kontrolliert. Sowohl für Brauereihefezellen als auch Bäckerhefezellen zeigte sich mit großen Glasperlen (Ø = 0,75 -1,5 mm) bereits nach 12 min ein mehr als 90proz. Zellaufschluß, während bei kleineren Glasperlen der Aufschluß noch unvollständig war. Das gewonnene Zellwandmaterial wurde an mikroporösen Membranen gewaschen, gefriergetrocknet und anschließend mit Enzymen umgesetzt. Proteasen zerstörten in der äußeren Zellwand die Proteinmatrix und setzten lösliches Mannan frei. Das unlösliche Glucan wurde durch Zentrifugieren abgetrennt und das Mannan durch Dialyse oder Chromatographie gereinigt.Bei Umsetzung mit Proteasen war vollständiger Umsatz ab einer Konzentration von 240 mg g -1 Zellwandmaterial in 26 h möglich. Zellwände aus Bäckerhefe mußten zuvor mit Petrolether extrahiert werden. Vo...

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“…It is a characteristic fungal cell wall constituent. It has been reported that fungi-derived (1 → 3)-β-D-glucan modulates various aspects of immunity [25–28]. Aside from fungi, dialysis membranes and filters made from cellulose are occasionally reported to contain (1 → 3)-β-D-glucan that may be solubilized during use.…”

Section: Discussionmentioning

confidence: 99%

Biocompatibility study of different hyaluronan products for intra-articular treatment of knee osteoarthritis

Yoshioka

Katayama

Nishiyama

et al. 2019

BMC Musculoskelet Disord

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Background Intra-articular (IA) injection of hyaluronic acid (HA) (IA-HA) is a well-recognized treatment option for pain associated with symptomatic knee osteoarthritis (OA). IA-HA products differ in their HA content, molecular weight, cross-linking, and source of HA. These differences are assumed to affect the biocompatibility of the IA-HA products once injected inside the knee joint. Methods In the present study, we investigated the biocompatibility of three multiple-injection IA-HA products available in the global market. These included SUPARTZ FX™, a medium range molecular weight HA derived from rooster comb (Avian-HA); ORTHOVISC®, a high range molecular weight HA obtained through biological fermentation (Bio-HA); and SYNVISC®, a high molecular weight cross-linked hyaluronan derived from rooster comb (Avian-CL-HA). Rabbit knee joint tissues were histologically and biochemically examined after IA injection of the products. Furthermore, we compared the amounts of impurities in the IA-HA products. Results IA injection of Avian-CL-HA into rabbit knee joints induced the aggregation of inflammatory cells, infiltration of eosinophils, and an increase in the number of cells in the synovial fluid. However, these effects were not seen in the Avian-HA and Bio-HA groups. The residual protein content and the contaminant levels of bacterial endotoxins were below the limit of quantitation in all HA products. Avian-CL-HA contained relatively a large amount of (1 → 3)-β-D-glucan, but this was below the lower limit of quantification in the other HA products. Conclusions The present results clearly demonstrate that the biocompatibility of Avian-HA is comparable to that of Bio-HA, and they were both considered to have a favorable safety profile for the treatment of symptomatic OA of the knee. However, immunostimulatory activity was observed after injection of Avian-CL-HA: this might be a result of its unique cross-linking structure and/or the considerable amount of (1 → 3)-β-D-glucan impurity present in the formulation.

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Development of natural product (1 → 3)‐β‐D‐glucan polymers as immune‐stimulating pharmaceuticals

Cited by 10 publications

References 28 publications

Polymer analytical characterization of glucan and mannan from yeast Saccharomyces cerevisiae

Polymer analytical characterization of glucan and mannan from yeast Saccharomyces cerevisiae

Mild enzymatic isolation of mannan and glucan from yeast Saccharomyces cerevisiae

Biocompatibility study of different hyaluronan products for intra-articular treatment of knee osteoarthritis

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