Mucin structural interactions with an alginate oligomer mucolytic in cystic fibrosis sputum

Pritchard, Manon F., Oakley, Juliette L., Brilliant, Charles D., Rye, Philip D., Forton, Julian, Doull, Iolo J. M., Ketchell, Ian, Hill, Katja E., Thomas, David W. and Lewis, Paul D. 2019. Mucin structural interactions with an alginate oligomer mucolytic in cystic fibrosis sputum. Vibrational Spectroscopy 103 , 102932. 10.1016/j.vibspec.2019.102932

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Abstract

Cystic fibrosis (CF) is an autosomal recessive, life-limiting condition characterized by progressive lung disease, which is a major cause of morbidity and mortality for these patients. The inhalation therapy, OligoG CF-5/20, is a low molecular weight (mean Mn 3200 g/mol) alginate oligomer, with a high guluronic acid content (>85%). The ability of OligoG CF-5/20 to enhance the activity of antimicrobial/antibiotic therapies, modify the rheological properties of CF sputum and interact with mucin, has previously been shown. To further characterize the physicochemical interactions of OligoG CF-5/20 with CF sputum, Fourier-transform infrared (FTIR) spectroscopy was used to analyze ex vivo sputum samples from adolescent CF patients (n = 13) following treatment with 0.2% OligoG CF-5/20. FTIR analysis confirmed the interaction of OligoG CF-5/20 with mucin glycans in CF sputum, which showed a shift in wavenumber from 1078 cm−1 to 1070 cm-1 and subsequent loss of the 1053 cm−1 peak in the OligoG CF-5/20 treated samples. OligoG CF-5/20 interaction with key terminal moieties in mucin were also evident, with a significant change in sulphation at wavenumber 1116 cm−1, suggesting a link with sulphated Lewis x antigen. There were also significant shifts at wavenumber 1637 cm-1 indicative of β-sheet conformational changes in the mucin peptide caused by action of OligoG. The alterations in charge of glycan and mucin structures support previous observations wherein OligoG CF-5/20 modifies the viscoelastic properties of CF sputum. These findings suggest a possible mechanism of action for the rheological changes observed with this novel therapy.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry Medicine
Publisher:	Elsevier
ISSN:	0924-2031
Date of First Compliant Deposit:	5 July 2019
Date of Acceptance:	11 June 2019
Last Modified:	05 Jul 2019 10:35
URI:	http://orca.cf.ac.uk/id/eprint/123903

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