Single molecule investigation of the onset and minimum size of the calcium-mediated junction zone in alginate

Bowman, Kate A.; Aarstad, Olav Andreas; Nakamura, Marcela; Stokke, Bjørn Torger; Skjåk‐Bræk, Gudmund; Round, Andrew N.

doi:10.1016/j.carbpol.2016.04.043

Cited by 26 publications

(30 citation statements)

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“…Although alginates in general do have calcium chelating ability, guluronate oligomers specifically have an increased ability to bind calcium in vitro compared to M oligomers [38]. Several studies have demonstrated that low molecular weight guluronate oligomers are particularly proficient at sequestering calcium [39,40] including OligoG [41]. OligoG may be acting as a calcium chelating agent which substitutes for the missing bicarbonate in the CF intestinal environment, sequestering calcium away from the packed mucins that are secreted into the intestine and allowing the mucus to expand, mature and disperse.…”

Section: Discussionmentioning

confidence: 97%

A novel guluronate oligomer improves intestinal transit and survival in cystic fibrosis mice

Vitko

Valerio

Rye

et al. 2016

Journal of Cystic Fibrosis

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Section: Discussionmentioning

confidence: 97%

A novel guluronate oligomer improves intestinal transit and survival in cystic fibrosis mice

Vitko

Valerio

Rye

et al. 2016

Journal of Cystic Fibrosis

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“…A recent publication further suggests that G-blocks must contain at least 8 G-subunits in order to accommodate calcium ions in an egg-box fashion, but on the other hand G-blocks must be shorter than 20 units because the longer molecules take considerably longer to form an egg-box with calcium. 13 Thus any potential drug candidate has to be readily soluble in the hydrophilic mucus while binding calcium. M-rich polymers have a tendency to self-aggregate and become relatively larger than MG-rich polymers.…”

Section: Discussionmentioning

confidence: 99%

“…MG12 (11)(12)(13) in the same way. The poly-M fraction had no detaching effect, whereas the MG12 caused some detachment at the highest concentration, 3% ( Figure 4D).…”

Section: Purified Alginate Polysaccharide Fractionsmentioning

confidence: 99%

“…We applied the fractions described in Fig. S1 with 6 (5-7), 12 (12)(13)(14)(15) or 20 (19)(20)(21)(22)(23)(24) G units (size range in parenthesis) to the apical side of CF mouse ileal explants ( Figure 4A). There was a tendency that 1.5% G6 detached the mucus, but the difference in mucus thickness pre and post aspiration was not significant ( Figure 4B).…”

Section: Purified Alginate Polysaccharide Fractionsmentioning

confidence: 99%

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OligoG CF‐5/20 normalizes cystic fibrosis mucus by chelating calcium

Ermund

Recktenwald

Skjåk‐Bræk

et al. 2017

Clin Exp Pharma Physio

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The goal of this study was to determine whether the guluronate (G) rich alginate OligoG CF-5/20 (OligoG) could detach cystic fibrosis (CF) mucus by calcium chelation, which is also required for normal mucin unfolding. Since bicarbonate secretion is impaired in CF, leading to insufficient mucin unfolding and thereby attached mucus, and since bicarbonate has the ability to bind calcium, we hypothesized that the calcium chelating property of OligoG would lead to detachment of CF mucus. Indeed, OligoG could compete with the N-terminus of the MUC2 mucin for calcium binding as shown by microscale thermophoresis. Further, effects on mucus thickness and attachment induced by OligoG and other alginate fractions of different length and composition were evaluated in explants of CF mouse ileum mounted in horizontal Ussing-type chambers. OligoG at 1.5% caused effective detachment of CF mucus and the most potent alginate fraction tested, the poly-G fraction of about 12 residues, had similar potency compared to OligoG whereas mannuronate-rich (M) polymers had minimal effect. In conclusion, OligoG binds calcium with appropriate affinity without any overt harmful effect on the tissue and can be exploited for treating mucus stagnation.

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“…46,47 HPAEC PAD chromatograms and NMR spectra of the oligoGs were presented previously. 48 Guluronic acid fractions with n = 6 and n = 16-18, and a mannuronic acid fraction with n = 10 were selected for conjugation to short PEG polymers using a reducing-end-selective method 49 previously shown to link polysaccharides to AFM probes and substrates. 50 For this conjugation, 0.5 mL of 5 M NaBH 3 CN (5.0 M solution of sodium cyanoborohydride in aqueous 1 M sodium hydroxide, Sigma-Aldrich), 0.1 mL of 0.5 mM oligosaccharide, 0.25 mL of 0.5 mM amino-PEG-Boc (3000 Da; polydispersity index 1.03) and 1.5 mL of MQ-water were mixed and incubated for 48-144 h. Gel Permeation Chromatography shows that the conjugate has a mass of ∼3600 Da, close to the expected mass of ∼4200 Da (for details of this analysis see ESI †).…”

Section: Methodsmentioning

confidence: 99%

Polymer sequencing by molecular machines: a framework for predicting the resolving power of a sliding contact force spectroscopy sequencing method

et al. 2017

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We evaluate an AFM-based single molecule force spectroscopy method for mapping sequences in otherwise difficult to sequence heteropolymers, including glycosylated proteins and glycans. The sliding contact force spectroscopy (SCFS) method exploits a sliding contact made between a nanopore threaded over a polymer axle and an AFM probe. We find that for sliding α-and β-cyclodextrin nanopores over a wide range of hydrophilic monomers, the free energy of sliding is proportional to the sum of two dimensionless, easily calculable parameters representing the relative partitioning of the monomer inside the nanopore or in the aqueous phase, and the friction arising from sliding the nanopore over the monomer.Using this relationship we calculate sliding energies for nucleic acids, amino acids, glycan and synthetic monomers and predict on the basis of these calculations that SCFS will detect N-and O-glycosylation of proteins and patterns of sidechains in glycans. For these applications, SCFS offers an alternative to sequence mapping by mass spectrometry or newly-emerging nanopore technologies that may be easily implemented using a standard AFM.

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Single molecule investigation of the onset and minimum size of the calcium-mediated junction zone in alginate

Cited by 26 publications

References 50 publications

A novel guluronate oligomer improves intestinal transit and survival in cystic fibrosis mice

A novel guluronate oligomer improves intestinal transit and survival in cystic fibrosis mice

OligoG CF‐5/20 normalizes cystic fibrosis mucus by chelating calcium

Polymer sequencing by molecular machines: a framework for predicting the resolving power of a sliding contact force spectroscopy sequencing method

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